Long-Read Sequencing is Required for Precision Diagnosis of Incontinentia Pigmenti

Long-Read Sequencing is Required for Precision Diagnosis of Incontinentia Pigmenti | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (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;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Brief Communication Long-Read Sequencing is Required for Precision Diagnosis of Incontinentia Pigmenti Monica Wojcik, Robin Clark, Abdallah Elias, Casie Genetti, Jill Madden, and 22 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5811417/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Incontinentia pigmenti (IP) is caused by loss-of-function variants in IKBKG, with molecular genetic diagnosis complicated by a pseudogene. We describe seven individuals from three families with IP but negative clinical testing in whom long-read sequencing identified causal variants. Concurrent methylation analysis explained disease severity in one individual who died from neurologic complications, identified a mosaic variant in an individual with an atypical presentation, and confirmed skewed X-chromosome inactivation in an XXY individual. Biological sciences/Biological techniques/Genomic analysis Health sciences/Diseases Full Text Additional Declarations Yes there is potential Competing Interest. MHW has consulted for Illumina and Sanofi and received speaking honoraria from Illumina, Sanofi, and GeneDx. DEM is engaged in a research agreement with Oxford Nanopore Technologies (ONT), is on a scientific advisory board at ONT and Basis Genetics, has received travel support from ONT and Pacific Biosciences, and holds stock options in MyOme and Basis Genetics. Individuals from Family 1 were enrolled in the Manton Center for Orphan Disease Research, under a protocol approved by the Boston Children's Hospital IRB. Individuals from Family 2 were recruited using a protocol approved by the University of Washington IRB: protocol 7064 (University of Washington, Repository for Mendelian Disorders). Individuals from Family 3 were recruited using a protocol approved by the University of Washington IRB: protocol 20161 (University of Washington, Genomic Discovery Initiative). All participants or their legal guardian provided written consent. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5811417","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Brief Communication","associatedPublications":[],"authors":[{"id":404605280,"identity":"c738d903-ec09-4928-8051-b083ab01e781","order_by":0,"name":"Monica Wojcik","email":"","orcid":"","institution":"Boston Children’s Hospital and Harvard Medical School","correspondingAuthor":false,"prefix":"","firstName":"Monica","middleName":"","lastName":"Wojcik","suffix":""},{"id":404605281,"identity":"6ba34f9c-c597-46d5-bc3f-ffa4746ac561","order_by":1,"name":"Robin 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MHW has consulted for Illumina and Sanofi and received speaking honoraria from Illumina, Sanofi, and GeneDx. DEM is engaged in a research agreement with Oxford Nanopore Technologies (ONT), is on a scientific advisory board at ONT and Basis Genetics, has received travel support from ONT and Pacific Biosciences, and holds stock options in MyOme and Basis Genetics.\u003c/p\u003e\n\u003cp\u003eIndividuals from Family 1 were enrolled in the Manton Center for Orphan Disease Research, under a protocol approved by the Boston Children's Hospital IRB. Individuals from Family 2 were recruited using a protocol approved by the University of Washington IRB: protocol 7064 (University of Washington, Repository for Mendelian Disorders). Individuals from Family 3 were recruited using a protocol approved by the University of Washington IRB: protocol 20161 (University of Washington, Genomic Discovery Initiative). 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