Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman

Identification of Pathogenic PKHD1 Variants in... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/14-1212" }, "headline": "Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from...", "datePublished": "2025-11-05T17:06:21", "dateModified": "2026-04-24T09:13:49", "author": [ { "@type": "Person", "name": "Intisar Al Alawi" }, { "@type": "Person", "name": "Maha Al Awadi" }, { "@type": "Person", "name": "Fatma Al Awaid" }, { "@type": "Person", "name": "Joshua Pillai" }, { "@type": "Person", "name": "Matthew Sampson" }, { "@type": "Person", "name": "Juliana E. Arcila Galvis" }, { "@type": "Person", "name": "Ashwaq Al Maimani" }, { "@type": "Person", "name": "Zainab Al Hashmi" }, { "@type": "Person", "name": "John A. Sayer" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Background Autosomal recessive polycystic kidney disease (ARPKD) is a rare, inherited disorder primarily affecting the kidneys and liver. Disease-causing variants in PKHD1 lead to a disruption of the encoded protein fibrocystin/polyductin. This study aims to identify disease causing variants in PKHD1 in families from the Dhofar region of Oman. Methods We conducted a case series of six families with antenatal diagnoses of ARPKD and postnatal deaths. Genetic testing was performed on neonates using Sanger sequencing and next-generation sequencing (NGS) to detect variants in PKHD1. In silico analysis of mutational consequences was performed. Results 5 distinct homozygous variants in the PKHD1 gene were identified, including three pathogenic frameshift variants (c.6111_6112delTT, c.7011dupT and c.9550dupT), a nonsense variant (c.340C>T) and a homozygous deletion spanning exons 58-60 of the PKHD1. These alleles have not been reported in previous studies. In silico modelling identified pathogenic alleles, predicted to lead to either truncated protein products or nonsense-mediated decay. Discussion Our findings identify disease causing PKHD1 variants in this genetically distinct Dhofar population, potentially due to factors such as geographical isolation, consanguinity, and founder effects. The identification of previously undescribed variants underscores the need for regional genetic studies in understanding ARPKD and its genotype-phenotype correlations. Conclusion This study reveals distinct PKHD1 disease-causing variants in the Dhofar region of Oman, contributing to the broader genetic understanding of ARPKD. These findings highlight the value of region-specific genetic research in identifying new disease causing variants. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-1212/v1", "name": "Identification of Pathogenic PKHD1 Variants in Infants with Autosomal..." } } ] } Home Browse Identification of Pathogenic PKHD1 Variants in Infants with Autosomal... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Al Alawi I, Al Awadi M, Al Awaid F et al. Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.12688/f1000research.171123.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] Intisar Al Alawi https://orcid.org/0000-0002-6674-7276 1 , Maha Al Awadi 2 , Fatma Al Awaid 2 , [...] Joshua Pillai https://orcid.org/0000-0002-2477-1868 3 , Matthew Sampson 3,4 , Juliana E. Arcila Galvis 5 , Ashwaq Al Maimani https://orcid.org/0009-0009-4695-9448 1 , Zainab Al Hashmi 1 , John A. Sayer https://orcid.org/0000-0003-1881-3782 3,5-7 Intisar Al Alawi https://orcid.org/0000-0002-6674-7276 1 , Maha Al Awadi 2 , [...] Fatma Al Awaid 2 , Joshua Pillai https://orcid.org/0000-0002-2477-1868 3 , Matthew Sampson 3,4 , Juliana E. Arcila Galvis 5 , Ashwaq Al Maimani https://orcid.org/0009-0009-4695-9448 1 , Zainab Al Hashmi 1 , John A. Sayer https://orcid.org/0000-0003-1881-3782 3,5-7 PUBLISHED 05 Nov 2025 Author details Author details 1 National Genetic Centre, Ministry of Health, Muscat, Oman 2 Sultan Qaboos Hospital, Ministry of Health, Salalah, Oman 3 Division of Pediatric Nephrology, Boston Children's Hospital, Boston, MA, USA 4 Harvard Medical School, Boston, Massachusetts, USA 5 Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UK 6 Renal Services, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, England, UK 7 NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, England, UK Intisar Al Alawi Roles: Data Curation, Formal Analysis, Investigation, Writing – Original Draft Preparation Maha Al Awadi Roles: Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation Fatma Al Awaid Roles: Investigation, Methodology, Writing – Original Draft Preparation Joshua Pillai Roles: Investigation, Methodology, Software, Visualization Matthew Sampson Roles: Investigation, Supervision, Validation Juliana E. Arcila Galvis Roles: Investigation, Validation, Writing – Review & Editing Ashwaq Al Maimani Roles: Investigation, Supervision, Writing – Original Draft Preparation Zainab Al Hashmi Roles: Investigation, Supervision, Writing – Original Draft Preparation John A. Sayer Roles: Funding Acquisition, Investigation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Genomics and Genetics gateway. Abstract Background Autosomal recessive polycystic kidney disease (ARPKD) is a rare, inherited disorder primarily affecting the kidneys and liver. Disease-causing variants in PKHD1 lead to a disruption of the encoded protein fibrocystin/polyductin. This study aims to identify disease causing variants in PKHD1 in families from the Dhofar region of Oman. Methods We conducted a case series of six families with antenatal diagnoses of ARPKD and postnatal deaths. Genetic testing was performed on neonates using Sanger sequencing and next-generation sequencing (NGS) to detect variants in PKHD1. In silico analysis of mutational consequences was performed. Results 5 distinct homozygous variants in the PKHD1 gene were identified, including three pathogenic frameshift variants (c.6111_6112delTT, c.7011dupT and c.9550dupT), a nonsense variant (c.340C>T) and a homozygous deletion spanning exons 58-60 of the PKHD1. These alleles have not been reported in previous studies. In silico modelling identified pathogenic alleles, predicted to lead to either truncated protein products or nonsense-mediated decay. Discussion Our findings identify disease causing PKHD1 variants in this genetically distinct Dhofar population, potentially due to factors such as geographical isolation, consanguinity, and founder effects. The identification of previously undescribed variants underscores the need for regional genetic studies in understanding ARPKD and its genotype-phenotype correlations. Conclusion This study reveals distinct PKHD1 disease-causing variants in the Dhofar region of Oman, contributing to the broader genetic understanding of ARPKD. These findings highlight the value of region-specific genetic research in identifying new disease causing variants. READ ALL READ LESS Keywords PKHD1, Autosomal Recessive Polycystic Kidney Disease, Dhofar, Consanguinity, Genetic heterogeneity, Oman Corresponding Author(s) John A. Sayer ( [email protected] ) Close Corresponding author: John A. Sayer Competing interests: No competing interests were disclosed. Grant information: J.A.G. is funded by MRC (MR/Y007808/1). J.A.S. is funded by LifeArc, Medical Research Council (MR/Y007808/1), Kidney Research UK (Paed_RP_001_ 20180925, RP_007_20210729), the Northern Counties Kidney Research Fund (20/01) and the European Union’s Horizon Europe research and innovation programme and from UKRI under grant agreement No: 101080717 (TheRaCil). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Al Alawi I et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Al Alawi I, Al Awadi M, Al Awaid F et al. Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.12688/f1000research.171123.1 ) First published: 05 Nov 2025, 14 :1212 ( https://doi.org/10.12688/f1000research.171123.1 ) Latest published: 24 Apr 2026, 14 :1212 ( https://doi.org/10.12688/f1000research.171123.2 )  There is a newer version of this article available. Suppress this message for one day. Introduction Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common recessively inherited cystic kidney disorders, with an estimated incidence ranging from 1 in 6,000 to 1 in 55,000 live births ( Zerres, Hansmann et al. 1988 , Guay-Woodford, Bissler et al. 2014 , Bergmann, Guay-Woodford et al. 2018 ). ARPKD most commonly presents in the neonatal and infantile period. It is characterized by progressive renal cystic dysplasia, which leads to enlarged, echogenic kidneys and varying degrees of renal impairment, as well as congenital hepatic fibrosis, which may progress to portal hypertension and its complications. Pulmonary hypoplasia due to oligohydramnios is a frequent and often life-threatening feature in perinatal presentations. While ARPKD is classically thought of as a disease of infancy and childhood, there is increasing recognition of later-onset and even adult presentations, in which renal and hepatic manifestations may be milder, slowly progressive, or discovered incidentally. The clinical spectrum therefore ranges from perinatal lethality to survival into adulthood with chronic kidney disease, portal hypertension, or combined hepatorenal involvement. While there is no definitive cure, current treatments focus on managing symptoms and delaying disease progression ( Guay-Woodford, Bissler et al. 2014 ). Disease-causing variants in PKHD1 , which encodes the fibrocystin/polyductin protein, impair the development of the kidney and bile ducts. Defects in fibrocystin lead to kidney cyst formation and malformation of bile ducts in the liver, resulting in polycystic kidneys and congenital hepatic fibrosis. Truncating mutations in PKHD1 often result in severe neonatal outcomes, reflecting a genotype-phenotype correlation ( Burgmaier, Brinker et al. 2021 ). Although ARPKD has been widely studied in various populations, the genetic diversity of this disorder in Oman remains inadequately understood. Prior studies have identified several disease-causing variants in the PKHD1 gene within the Omani population, but these studies did not focus on the Dhofar region ( Al Alawi, Molinari et al. 2020 ). The Dhofar region’s geographic isolation ( Figure 1 ), bordered by mountains and deserts, has fostered a unique demographic marked by consanguinity and minimal gene flow ( Rajab, Hamza et al. 2015 ). Figure 1. Geographical map of Oman and the Dhofar region. Map (drawn using https://www.mapchart.net/ and licensed under a Creative Commons Attribution-ShareAlike 4.0 International License .) showing Dhofar region (Dhofar Governorate) in the south of Oman. It is the largest of 11 governorates in Oman in terms of area with a population of around 500,000 people. Here we present a case series to investigate disease-causing PKHD1 variants identified in neonates from six families in the Dhofar region. The study aims to expand the genetic landscape of ARPKD in Oman and contribute to the broader understanding of this rare genetic disorder. Methods Ethical approvals and patients’ inclusion and clinical evaluation This case series includes six families from the Dhofar region of Oman who were referred to the National Genetic Centre at the Royal Hospital, Oman, following antenatal diagnoses of ARPKD. All families had neonates with multiple congenital anomalies, including bilateral renal abnormalities, pulmonary hypoplasia, and oligohydramnios. This study was ethically approved by the Royal Hospital Research Etical Committee, Ministry of Health, Oman (MOH/CSR/21/24412). For genetic studies of patients, written informed consent was provided by the parents of all affected neonates. Patient selection The six families included in this study were referred to the National Genetic Centre at Royal Hospital, Oman, based on antenatal findings of congenital anomalies consistent with ARPKD. The clinical features included: oligohydramnios, bilateral kidney enlargement, pulmonary hypoplasia, and multiple congenital anomalies (e.g., dysmorphic features such as low-set ears, box-shaped head, and sandal gap deformity). The clinical presentation, including prenatal ultrasound findings, birth details, and postnatal progress, was recorded. Neonatal deaths occurred within 48 hours postpartum in all cases, which provided an opportunity for genetic analysis from post-mortem DNA samples. Additionally, clinical investigations included antenatal ultrasound scanning where the prenatal diagnosis of ARPKD was based on ultrasound findings showing enlarged and echogenic kidneys, absent bladder, and oligohydramnios. Postnatal clinical observations were performed on arrival at the Special Care Baby Unit (SCBU), where the neonates were monitored for respiratory distress (grunting, cyanosis, and decreased oxygen saturation), and vital signs were recorded. The clinical progress for each family such as gestational age at delivery, birth weight and vital signs (e.g., heart rate, blood pressure, oxygen saturation, and temperature) was documented. DNA isolation, library preparation and next generation sequencing DNA samples for genetic analysis were extracted from cord blood/post-mortem blood specimens and archived at the National Genetic Centre for subsequent analysis. Clinical information was gathered from medical records, including antenatal ultrasound findings, birth outcomes, and postnatal management. Genetic testing was performed using both Sanger sequencing and next-generation sequencing (NGS) to identify mutations in the PKHD1 gene ( Al Alawi, Al Salmi et al. 2019 ). For Sanger sequencing, target regions were amplified using AmpliTaq Gold 360 Master Mix kit (Applied Biosystems) using gene specific oligonucleotide primers. For NGS, a multiplex PCR approach amplified 4898 amplicons from 60 target genes (including GANAB , HNF1B , NOTCH2 , PKD1 , and PKD2 , among others) using a custom QIAseq panel (Qiagen). Subsequent NGS was performed on an Illumina MiSeq system. The resulting data (vcf files) was processed through Variant Studio software to allow nucleotide variant and copy number variant calling. All variant nomenclature followed the standards set by the Human Genome Variation Society guidelines and confirmed via Sanger sequencing. PKHD1 frameshift variants leading to predicted downstream nonsense alleles were modelled using MutationTaster2025 ( https://www.genecascade.org/MutationTaster2025/ ) and sequences are shown in Extended Data. Computational protein structure prediction The wild-type structure of fibrocystin was predicted with AlphaFold3 ( Abramson, Adler et al. 2024 ) where the overall structure was of high confidence (pLDDT = 73.59). To model the frameshift and duplication variants, we predicted their complete structure and superimposed it on the wild-type. PyMOL was used for visualization ( Schrödinger and DeLano 2020 ). Results Clinical and molecular genetic findings We analyzed six families with neonates affected by ARPKD. The clinical presentation of the affected neonates included signs of oligohydramnios, bilateral enlarged kidneys, pulmonary hypoplasia, and other dysmorphic features. All neonates died within 48 hours postpartum, with no survival beyond seven days. Table 1 illustrates the clinical presentation and outcomes of the affected neonates. The clinical progress for each family such as gestational age at delivery, birth weight and vital signs (e.g., heart rate, blood pressure, oxygen saturation, and temperature) was documented. The gestational age at delivery in our families ranged between 32 and 36 weeks, while the birth weight ranged from 2.3 kg to 3.4 kg. Table 2 summarizes these critical postnatal data. Table 1. Clinical presentation and outcomes of affected neonates. Family Gestational age (weeks) Birth weight (kg) Key clinical features PKHD1 variant Outcome Family 1, affected female 34 2.36 Oligohydramnios, bilateral renal enlargement, pulmonary hypoplasia, weak cry, gasping, cyanosis, dysmorphic features. Homozygous c.7011dupT; p.(Gly2338Trpfs*41) Chr6:51887230_51887231insA (GRCh38) Expired within 48 hours Family 2, affected female 33 2.36 Multiple congenital anomalies, oligohydramnios, breech presentation, pulmonary hypoplasia, bilateral kidney masses. Homozygous c.7011dupT; p.(Gly2338Trpfs*41) Chr6:51887230_51887231insA (GRCh38) Expired within 48 hours Family 3, affected male 35 2.40 Polycystic kidneys, pulmonary hypoplasia, pneumothorax, dysmorphic features. Homozygous c.6111_6112delTT; p.(Leu2039fs*13) Chr6:51934120_51934121delAA (GRCh38) Expired within 7 hours Family 4 32 2.30 Multiple congenital anomalies, bilateral palpable kidney masses, dysmorphic features. Homozygous deletion exons 58-60 of PKHD1 Expired within 24 hours Family 5 36 2.36 Oligohydramnios, enlarged kidneys, pulmonary hypoplasia, dysmorphic features. Homozygous c.9550dupT; p.(Tyr3184Leufs*18) Chr6:51748065_51748066insA (GRCh38) Expired within 22 hours Family 6 32 3.40 Oligohydramnios, enlarged kidneys, pulmonary hypoplasia, dysmorphic features. Homozygous c.340C>T; p.Q114* Chr6:52079950G>A (GRCh38) Expired within 48 hours Table 2. Postnatal vital signs for affected neonates. Family Heart rate (bpm) Blood pressure (mmHg) Oxygen saturation (%) Respiratory rate (bpm) Temperature (°C) Family 1 140 73/42 70 70 36.2 Family 2 149 73/42 75 60 36.0 Family 3 147 73/42 70 70 36.0 Family 4 130 68/40 65 60 36.5 Family 5 140 72/40 65 65 36.2 Family 6 N/A N/A N/A N/A N/A Each of the six families described had a molecular genetic diagnosis of ARPKD secondary to biallelic PKHD1 disease causing variants ( Figure 2 ) and are summarized below. Figure 2. Genetic analysis of novel PKHD1 variants. (a) The functional regions of fibrocystin, including the IPT, PA14, G8, PbH1, CST, and NLS domains. (b) Sanger sequencing of the c.340C>T, c.6111_6112delTT, c.7011dupT, c.9550dupT variants. The sequence for c.7011dupT of the patient is unavailable and instead displayed for the heterozygote parent. (c) The pedigree diagrams for all six Omani families. Squares, males; Circles, females; Shaded, affected. (d) Position of novel mutations on the wild-type structure of fibrocystin. Family 1 included a female infant born at 34 weeks of gestation to consanguineous parents presented antenatally with bilateral enlarged kidneys and pulmonary hypoplasia. The infant died within 48 hours. Genetic testing identified a homozygous frameshift mutation, PKHD1 c.7011dupT; p.(G2338WfsX41), classified as likely pathogenic. There was a previous history of 3 neonatal deaths with similar clinical presentations. Family 2 included a female infant, born at 33 weeks of gestation via breech delivery, had bilateral enlarged kidneys and pulmonary hypoplasia and died within 48 hours. Genetic analysis confirmed a homozygous frameshift mutation, PKHD1 c.7011dupT; p.(G2338WfsX41). There was a previous history of an early miscarriage. Family 3 included a male infant, born at 35 weeks of gestation, was diagnosed antenatally with polycystic kidneys and suspected Potter syndrome. The neonate died within 7 hours due to spontaneous pneumothorax. Genetic analysis confirmed a frameshift mutation (not present in gnomAD, ClinVar, Leiden Open Variation Database) PKHD1 : c.6111_6112delTT; p.(L2039fsX13). Family 4 included a male infant born at 32 weeks of gestation to consanguineous parents presented with bilateral enlarged kidneys and other dysmorphic features. Genetic analysis revealed a novel homozygous deletion spanning exons 58-60 of the PKHD1 gene, classified as likely pathogenic. Family 5 included a second twin from a consanguineous couple, born at 36 weeks, presented with oligohydramnios and bilateral kidney enlargement. The neonate died within 22 hours postpartum. A novel frameshift variant, PKHD1 c.9550dupT; p.(Y3184LfsX18), was identified. Family 6: A male infant was born at 32 weeks of gestation to consanguineous parents presented with oligohydramnios and bilateral kidney enlargement. A homozygous nonsense variant, PKHD1 c.340C>T; p.(Q114*) was identified. In silico modelling of novel PKHD1 variants In Figure 3 , we have displayed the predicted protein structures for the five novel PKHD1 variants superimposed onto the wild-type fibrocystin structure. The c.340C>T results in a nonsense Q114X variant that encodes for the complete IPT 1 domain ( Figure 3a ) but causes a loss of most of its wild-type structure ( Figure 3b ). The c.6111_6112delTT is predicted to cause a L2039fsX13 frameshift, impacting the G8 1 domain ( Figure 3c ). The wild-type G8 1 domain is composed of 10 β-strands and one α-helix ( He, Liu et al. 2006 ). In our structural model ( Figure 3d ), we observed these structural characteristics, but an additional β-strand is formed resulting from the frameshift. The c.7011dupT mutation is predicted to result in a G2338WfsX41 frameshift, where the PbH1 domain is affected ( Figure 3e ). The wild-type PbH1 domain is composed of 3 β-strands stacked into six repeats ( Mayans, Scott et al. 1997 ). In the mutant structure, PbH1 1 to PbH1 4 is normal, but the frameshift results in a loss of the remaining two repeats and instead a structure composed of a loop and α-helix is formed ( Figure 3f ). Lastly, the c.9550dupT (Y3184LfsX18) is located on an unknown region of fibrocystin ( Figure 3g ), where the frameshift does not form secondary structure, and the C-terminal region is lost ( Figure 3h ). Figure 3. In silico modelling of PKHD1 variants. (a) The c.340C>T mutation is predicted to cause a Q114X nonsense variant, (b) where the mutant structure only partially encodes for the IPT one domain compared to the wild-type structure. (c) The c.6111_6112delTT leads to L2039fsX13, impacting the G8 1 domain, and (d) encoding nearly half of the wild-type structure. (e) The c.7011dupT cause a G2338WfsX41 frameshift, (f ) where PbH1 is partially lost. (g) Lastly, the c.9550dupT leads to Y3184LfsX18, encoding an unknown domain of PKHD1 (h) close to the C-terminal region. Discussion The universal presence of pulmonary hypoplasia in these neonates aligns with ARPKD’s hallmark features and is often associated with Potter syndrome due to oligohydramnios ( Guay-Woodford, Bissler et al. 2014 ). The severity of oligohydramnios and lung underdevelopment could explain the early mortality observed in these cases. Despite genetic heterogeneity, the clinical presentations were remarkably consistent, with common features such as bilateral kidney enlargement and dysmorphic features. This could point to a shared pathophysiological mechanism linked to the PKHD1 mutations in this population. This case series highlights the identification of five distinct mutations in the PKHD1 gene in neonates from the Dhofar region of Oman. The presence of a recurrent variant (c.7011dupT), a nonsense variant and three other novel variants (c.6111_6112delTT, c.9550dupT, and a large deletion) suggests significant genetic heterogeneity within the region. Notably, these alleles were not previously reported in studies of ARPKD in other parts of Oman ( Al Alawi, Molinari et al. 2020 ), indicating that the Dhofar population may harbor unique genetic variants. While previous studies of ARPKD in Oman have focused on more populous regions, this study uncovers significant genetic diversity within the Dhofar population. The identification of novel mutations, including c.6111_6112delTT and c.9550dupT, points to the complex genetic architecture of ARPKD in Oman, which may be influenced by regional variations in genetic isolation and migration patterns. The Dhofar region, the southernmost governate of Oman, is geographically isolated by mountains and deserts, which likely restricts gene flow from neighboring populations. This isolation can contribute to the accumulation of distinct genetic mutations, as observed in the c.7011dupT allele in two families, who are likely to be related. This was also true for a CFTR allele reported in patients with cystic fibrosis that was also specific to this distinct geographical region ( Al Oraimi, Al Shidhani et al. 2022 ). The high rate of consanguinity in Dhofar (up to 68%, ( Al Oraimi, Al Shidhani et al. 2022 )) likely enhances the likelihood of genetic drift and the founder effect, potentially explaining the presence of this mutation in multiple families. Conclusion This study identifies five distinct PKHD1 mutations in neonates from the Dhofar region of Oman, contributing to the genetic understanding of ARPKD. Our findings underscore the need for regional studies to map Oman’s genetic diversity. Further research, including larger studies involving other regions of Oman, is necessary to better understand the molecular basis of ARPKD in this population and to inform genetic counseling and management strategies for affected families. Data availability Underlying data No underlying data associated with this article. Extended data Figshare: Extended data 1. https://doi.org/10.6084/m9.figshare.30188437.v1 . This project contains the following extended data: • Supplemental Material_PKHD1.docx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Details of sequence variants and clinical information have been deposited at Leiden Open Variation Database 3.0 ( https://www.lovd.nl ) ( Fokkema, Kroon, et al. 2021 ). • https://databases.lovd.nl/shared/individuals/00466658 • https://databases.lovd.nl/shared/individuals/00466578 • https://databases.lovd.nl/shared/individuals/00466580 • https://databases.lovd.nl/shared/individuals/00466582 • https://databases.lovd.nl/shared/individuals/00466585 • https://databases.lovd.nl/shared/individuals/00466581 Acknowledgements We thank the affected families, and their physicians who contributed to this study. References Abramson J, Adler J, Dunger J, et al. : Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature. 2024; 630 (8016): 493–500. PubMed Abstract | Publisher Full Text | Free Full Text Al Alawi I, Al Salmi I, Al Rahbi F, et al. : Molecular Genetic Diagnosis of Omani Patients With Inherited Cystic Kidney Disease. Kidney Int Rep. 2019; 4 (12): 1751–1759. PubMed Abstract | Publisher Full Text | Free Full Text Al Alawi I, Molinari E, Al Salmi I, et al. : Clinical and genetic characteristics of autosomal recessive polycystic kidney disease in Oman. BMC Nephrol. 2020; 21 (1): 347. PubMed Abstract | Publisher Full Text | Free Full Text Al Oraimi S, Al Shidhani K, Al Harthi H, et al. : Prevalence and Characteristics of Cystic Fibrosis in Omani Children: A Multi-center Cross-sectional Study. Oman Med. J. 2022; 37 (6): e444. PubMed Abstract | Publisher Full Text | Free Full Text Bergmann C, Guay-Woodford LM, Harris PC, et al. : Polycystic kidney disease. Nat. Rev. Dis. Primers. 2018; 4 (1): 50. PubMed Abstract | Publisher Full Text | Free Full Text Burgmaier K, Brinker L, Erger F, et al. : Refining genotype-phenotype correlations in 304 patients with autosomal recessive polycystic kidney disease and PKHD1 gene variants. Kidney Int. 2021; 100 (3): 650–659. PubMed Abstract | Publisher Full Text Fokkema IF, Kroon M, López Hernández JA, et al. : The LOVD3 platform: efficient genome-wide sharing of genetic variants. Eur. J. Hum. Genet. 2021; 29 : 1796–1803. PubMed Abstract | Publisher Full Text | Free Full Text Guay-Woodford LM, Bissler JJ, Braun MC, et al. : Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J. Pediatr. 2014; 165 (3): 611–617. PubMed Abstract | Publisher Full Text | Free Full Text He QY, Liu XH, Li Q, et al. : G8: a novel domain associated with polycystic kidney disease and non-syndromic hearing loss. Bioinformatics. 2006; 22 (18): 2189–2191. PubMed Abstract | Publisher Full Text Mayans O, Scott M, Connerton I, et al. : Two crystal structures of pectin lyase A from Aspergillus reveal a pH driven conformational change and striking divergence in the substrate-binding clefts of pectin and pectate lyases. Structure. 1997; 5 (5): 677–689. PubMed Abstract | Publisher Full Text Rajab A, Hamza N, Al Harasi S, et al. : Repository of mutations from Oman: The entry point to a national mutation database. F1000Res. 2015; 4 : 891. PubMed Abstract | Publisher Full Text | Free Full Text Schrödinger L, DeLano W: PYMOL.2020. Reference Source Zerres K, Hansmann M, Mallmann R, et al. : Autosomal recessive polycystic kidney disease. Problems of prenatal diagnosis. Prenat. Diagn. 1988; 8 (3): 215–229. PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 05 Nov 2025 ADD YOUR COMMENT Comment Author details Author details 1 National Genetic Centre, Ministry of Health, Muscat, Oman 2 Sultan Qaboos Hospital, Ministry of Health, Salalah, Oman 3 Division of Pediatric Nephrology, Boston Children's Hospital, Boston, MA, USA 4 Harvard Medical School, Boston, Massachusetts, USA 5 Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UK 6 Renal Services, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, England, UK 7 NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, England, UK Intisar Al Alawi Roles: Data Curation, Formal Analysis, Investigation, Writing – Original Draft Preparation Maha Al Awadi Roles: Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation Fatma Al Awaid Roles: Investigation, Methodology, Writing – Original Draft Preparation Joshua Pillai Roles: Investigation, Methodology, Software, Visualization Matthew Sampson Roles: Investigation, Supervision, Validation Juliana E. Arcila Galvis Roles: Investigation, Validation, Writing – Review & Editing Ashwaq Al Maimani Roles: Investigation, Supervision, Writing – Original Draft Preparation Zainab Al Hashmi Roles: Investigation, Supervision, Writing – Original Draft Preparation John A. Sayer Roles: Funding Acquisition, Investigation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information J.A.G. is funded by MRC (MR/Y007808/1). J.A.S. is funded by LifeArc, Medical Research Council (MR/Y007808/1), Kidney Research UK (Paed_RP_001_ 20180925, RP_007_20210729), the Northern Counties Kidney Research Fund (20/01) and the European Union’s Horizon Europe research and innovation programme and from UKRI under grant agreement No: 101080717 (TheRaCil). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) version 2 Revised Published: 24 Apr 2026, 14:1212 https://doi.org/10.12688/f1000research.171123.2 version 1 Published: 05 Nov 2025, 14:1212 https://doi.org/10.12688/f1000research.171123.1 Copyright © 2025 Al Alawi I et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Al Alawi I, Al Awadi M, Al Awaid F et al. Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.12688/f1000research.171123.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 05 Nov 2025 Views 0 Cite How to cite this report: Sergi CM. Reviewer Report For: Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.5256/f1000research.188677.r450003 ) The direct URL for this report is: https://f1000research.com/articles/14-1212/v1#referee-response-450003 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 29 Jan 2026 Consolato M Sergi , Children’s Hospital of Eastern Ontario, Ontario, Canada; Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada Approved VIEWS 0 https://doi.org/10.5256/f1000research.188677.r450003 Infants with autosomal recessive polycystic kidney disease (ARPKD) in the Dhofar region of Oman display unique, previously unreported homozygous PKHD1 mutations (e.g., c.6111_6112delTT, c.7011dupT, c.9550dupT, c.340C>T, and deletion of exons 58-60). These variations, frequently associated with consanguinity and founder effects, ... Continue reading READ ALL Infants with autosomal recessive polycystic kidney disease (ARPKD) in the Dhofar region of Oman display unique, previously unreported homozygous PKHD1 mutations (e.g., c.6111_6112delTT, c.7011dupT, c.9550dupT, c.340C>T, and deletion of exons 58-60). These variations, frequently associated with consanguinity and founder effects, generally result in shortened proteins or severe, early-onset diseases. Principal Discoveries Regarding PKHD1 in ARPKD Patients from Dhofar/Oman. The elevated prevalence of ARPKD in this location is ascribed to significant levels of consanguinity, geographical seclusion, and founder effects. These variations result in severe, early-onset ARPKD, frequently associated with a dismal prognosis, encompassing prenatal diagnosis and postnatal mortality. Given the detection of distinct, consistent variants throughout the population, targeted PCR investigation of these specific alleles is recommended for diagnosis. Al-Alawi et al. describe five unique homozygous variations in the PKHD1 gene. These variants were discovered, comprising three pathogenic frameshift variants (c.6111_6112delTT, c.7011dupT, and c.9550dupT), a nonsense variant (c.340C>T), and a homozygous deletion encompassing exons 58-60 of the PKHD1. These alleles have not been documented in prior research. In silico modeling showed either shortened protein products or nonsense-mediated degradation. Their research confirms the geographical isolation, consanguinity, and founder effects. These findings support the significance of region-specific genomic studies in uncovering novel pathogenic mutations. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Dorn L, Menezes L, Mikuz G, Otto H, et al.: Immunohistochemical detection of polyductin and co‐localization with liver progenitor cell markers during normal and abnormal development of the intrahepatic biliary system and in adult hepatobiliary carcinomas. Journal of Cellular and Molecular Medicine . 2009; 13 (7): 1279-1290 Publisher Full Text 2. Prelog M, Bergmann C, Ausserlechner M, Fischer H, et al.: Successful transplantation in a child with rapid progression of autosomal recessive polycystic kidney disease associated with a novel mutation. Pediatric Transplantation . 2006; 10 (3): 362-366 Publisher Full Text 3. Johnson C, Gissen P, Sergi C: Molecular pathology and genetics of congenital hepatorenal fibrocystic syndromes. Journal of Medical Genetics . 2003; 40 (5): 311-319 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: My group and I work on hepatorenal fibrocystic diseases. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sergi CM. Reviewer Report For: Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.5256/f1000research.188677.r450003 ) The direct URL for this report is: https://f1000research.com/articles/14-1212/v1#referee-response-450003 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Yang H. Reviewer Report For: Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.5256/f1000research.188677.r447908 ) The direct URL for this report is: https://f1000research.com/articles/14-1212/v1#referee-response-447908 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 13 Jan 2026 Hana Yang , Mayo Clinic Minnesota, Rochester, Minnesota, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.188677.r447908 This article is a well-written and thorough study. It describes six Omani families with children affected by ARPKD, highlighting the high consanguinity in this region, which makes a few PKHD1 mutations relatively common. The detailed analysis of potential structural disruptions ... Continue reading READ ALL This article is a well-written and thorough study. It describes six Omani families with children affected by ARPKD, highlighting the high consanguinity in this region, which makes a few PKHD1 mutations relatively common. The detailed analysis of potential structural disruptions in the PKHD1 protein is particularly impressive and adds significant value to the understanding of pathogenic mechanisms. Overall, the paper is clear, scientifically sound, and provides important insights. I strongly recommend this article for acceptance. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Genetics in polycystic kidney disease. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Yang H. Reviewer Report For: Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.5256/f1000research.188677.r447908 ) The direct URL for this report is: https://f1000research.com/articles/14-1212/v1#referee-response-447908 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 05 Nov 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 24 Apr 26 Version 1 05 Nov 25 read read Hana Yang , Mayo Clinic Minnesota, Rochester, USA Consolato M Sergi , Children’s Hospital of Eastern Ontario, Ontario, Canada; University of Alberta, Edmonton, Canada Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Sergi C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 29 Jan 2026 | for Version 1 Consolato M Sergi , Children’s Hospital of Eastern Ontario, Ontario, Canada; Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada 0 Views copyright © 2026 Sergi C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Infants with autosomal recessive polycystic kidney disease (ARPKD) in the Dhofar region of Oman display unique, previously unreported homozygous PKHD1 mutations (e.g., c.6111_6112delTT, c.7011dupT, c.9550dupT, c.340C>T, and deletion of exons 58-60). These variations, frequently associated with consanguinity and founder effects, generally result in shortened proteins or severe, early-onset diseases. Principal Discoveries Regarding PKHD1 in ARPKD Patients from Dhofar/Oman. The elevated prevalence of ARPKD in this location is ascribed to significant levels of consanguinity, geographical seclusion, and founder effects. These variations result in severe, early-onset ARPKD, frequently associated with a dismal prognosis, encompassing prenatal diagnosis and postnatal mortality. Given the detection of distinct, consistent variants throughout the population, targeted PCR investigation of these specific alleles is recommended for diagnosis. Al-Alawi et al. describe five unique homozygous variations in the PKHD1 gene. These variants were discovered, comprising three pathogenic frameshift variants (c.6111_6112delTT, c.7011dupT, and c.9550dupT), a nonsense variant (c.340C>T), and a homozygous deletion encompassing exons 58-60 of the PKHD1. These alleles have not been documented in prior research. In silico modeling showed either shortened protein products or nonsense-mediated degradation. Their research confirms the geographical isolation, consanguinity, and founder effects. These findings support the significance of region-specific genomic studies in uncovering novel pathogenic mutations. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Dorn L, Menezes L, Mikuz G, Otto H, et al.: Immunohistochemical detection of polyductin and co‐localization with liver progenitor cell markers during normal and abnormal development of the intrahepatic biliary system and in adult hepatobiliary carcinomas. Journal of Cellular and Molecular Medicine . 2009; 13 (7): 1279-1290 Publisher Full Text 2. Prelog M, Bergmann C, Ausserlechner M, Fischer H, et al.: Successful transplantation in a child with rapid progression of autosomal recessive polycystic kidney disease associated with a novel mutation. Pediatric Transplantation . 2006; 10 (3): 362-366 Publisher Full Text 3. Johnson C, Gissen P, Sergi C: Molecular pathology and genetics of congenital hepatorenal fibrocystic syndromes. Journal of Medical Genetics . 2003; 40 (5): 311-319 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise My group and I work on hepatorenal fibrocystic diseases. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Sergi CM. Peer Review Report For: Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.5256/f1000research.188677.r450003) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1212/v1#referee-response-450003 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Yang H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 13 Jan 2026 | for Version 1 Hana Yang , Mayo Clinic Minnesota, Rochester, Minnesota, USA 0 Views copyright © 2026 Yang H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article is a well-written and thorough study. It describes six Omani families with children affected by ARPKD, highlighting the high consanguinity in this region, which makes a few PKHD1 mutations relatively common. The detailed analysis of potential structural disruptions in the PKHD1 protein is particularly impressive and adds significant value to the understanding of pathogenic mechanisms. Overall, the paper is clear, scientifically sound, and provides important insights. I strongly recommend this article for acceptance. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Not applicable Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Genetics in polycystic kidney disease. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Yang H. Peer Review Report For: Identification of Pathogenic PKHD1 Variants in Infants with Autosomal Recessive Polycystic Kidney Disease from the Dhofar Region, Oman [version 1; peer review: 2 approved] . F1000Research 2025, 14 :1212 ( https://doi.org/10.5256/f1000research.188677.r447908) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-1212/v1#referee-response-447908 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "Identification of Pathogenic PKHD1 Variants...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/14-1212/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/14-1212/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/14-1212/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Al Alawi I et al.'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/14-1212/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/14-1212", templates : { twitter : "Identification of Pathogenic PKHD1 Variants in Infants with Autosomal.... Al Alawi I et al., published by " + "@F1000Research" + ", https://f1000research.com/articles/14-1212/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/171123/188677") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "188677"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "451478": 0, "451479": 0, "451476": 0, "451477": 0, "451474": 0, "451475": 0, "451472": 0, "451473": 0, "430622": 0, "430623": 0, "430621": 0, "451480": 0, "451481": 0, "447910": 0, "430630": 0, "447911": 0, "430628": 0, "447908": 19, "447909": 0, "430629": 0, "430626": 0, "430627": 0, "430624": 0, "430625": 0, "447916": 0, "447917": 0, "447914": 0, "447915": 0, "447912": 0, "447913": 0, "450006": 0, "450007": 0, "450004": 0, "450005": 0, "450002": 0, "450003": 8, "450001": 0, "478814": 0, "478813": 0, "450010": 0, "450008": 0, "450009": 0, "440807": 0, "440814": 0, "445806": 0, "440815": 0, "445807": 0, "440812": 0, "440813": 0, "440810": 0, "440811": 0, "440808": 0, "440809": 0, "445814": 0, "445815": 0, "445812": 0, "445813": 0, "445810": 0, "445811": 0, "440816": 0, "445808": 0, "445809": 0, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "de212a55-91a8-4a42-bafe-0770ce922541"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });