Premarital spinal muscular atrophy screening program results from a province in the Black Sea region of Turkiye: Two years of experience

Premarital spinal muscular atrophy screening program results from a province in the Black Sea region of Turkiye: Two years of experience | 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 Research Article Premarital spinal muscular atrophy screening program results from a province in the Black Sea region of Turkiye: Two years of experience Feyza Nur Topcu Yenercag, Günay Kaya Tarhan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5908427/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 Objective Spinal muscular atrophy (SMA) is a life-shortening autosomal recessive neuromuscular disease. In this study, the aim was to determine the use of premarital SMA carrier screening and the frequency of SMA carriers in this population. Study Design: The Premarital National SMA Carrier Screening Program was applied to 19,988 people between 27 December 2021 and 31 May 2024. Result A total of 453 people were found to be SMA carriers with heterozygote deletions in exon 7 of SMN1, indicating a carrier prevalence of approximately 1:44 (2.26%) in the population. After detailed genetic counseling, 441 partners were tested, and 13 were identified as SMA carriers. These couples were given information about preimplantation genetic diagnosis, and the birth of infants affected by SMA disease was prevented. Conclusion In our experience with carrier screening, awareness of premarital SMA carrier screening can be effectively maximized. Medical Genetics Spinal muscular atrophy Prenatal diagnosis Carrier screening SMN1 Introduction Spinal muscular atrophy (SMA) is a neuromuscular disease that is one of the most common genetic causes of infant mortality worldwide. Additionally, it is the second most common and deadly autosomal recessive disease ( 1 ). SMA frequently occurs with homozygotic deletion or mutation of the survival motor neuron (SMN) gene located on the 5th chromosome. If the SMN protein cannot be produced at adequate levels, degeneration of alpha motor neurons occurs, and atrophy develops in muscles ( 2 ). The most frequent mutation occurring in the SMN1 gene is deletion of exon 7, which is located on the 5th chromosome ( 3 ). SMA is frequently diagnosed late after symptoms appear, as it is a rare disease with heterogeneous findings. According to the results of a systematic review, the incidence of SMA worldwide is 10 per 100,000 live births. The prevalence was determined to be 1–3 per 100,000 people, with low detection rates thought to be related to the shortened life expectancy to a great degree ( 1 ). According to a multinational study investigating different ethnic groups, the SMA carrier frequency varies from 1:47–72 ( 4 ). In Turkiye, the incidence of SMA and carrier rates are not clearly known. However, it is thought that our country, with frequent consanguineous marriages, has high rates of autosomal recessive heritable diseases and carrier rates. Considering that nearly 1,100,000 live births have occurred per year in recent years, the annual new case number is predicted to range from 130–180 (mean: 150). Nearly 3000 SMA patients are monitored ( 5 ). The SMA is divided into 4 subtypes according to age at onset and severity of muscle weakness. SMA type 1 (Werdnig–Hoffman disease) is the earliest and most severe form, causing severe and progressive respiratory problems and hypotonia in the first 6 months of life. SMA type 2 (subacute form) generally begin at 6–18 months, with symptoms similar to those of type 1, although they do not worsen rapidly. SMA type 3 (Kugelberg–Welander disease) begins after the age of 2 years, and the first symptom is difficulty walking. Type 4 begins in adulthood and is the mildest form. Potential treatment approaches have been developed with the understanding that SMA disease has molecular genetic features ( 6 ). Two treatment methods (nusinersen and zolgensma) have received FDA approval and significantly increase quality of life in the long term ( 7 ). Therapeutic approaches are known to increase the level of SMN in motor neurons when applied presymptomatically. Therefore, early diagnosis and treatment can slow the neurodegenerative process ( 8 ). For genetic diseases, primary (screening of society for carriers, screening of populations at risk, premarital screening programs, preconception screening), secondary (neonatal screening programs (NSP), treatment of presymptomatic infants) and tertiary (treatment of symptomatic infants) protection are available. Owing to NSP, SMA disease is detected in the early period, and severe forms may be prevented with presymptomatic treatment. Health economy studies revealed that although the value of NSP was clearly revealed, a problem frequently reported in upper middle-income countries is the formation of a greater patient burden than the system can treat ( 9 ). This increases the importance of premarital screening (PMS), which prevents the birth of sick infants ( 10 ). A premarital SMA screening program is implemented throughout Turkiye. The aim of the program is to offer genetic counseling and prenatal or preimplantation diagnostic test options to couples identified as carriers. Additionally, the long-term target is to reduce morbidity and mortality associated with SMA ( 5 ). In this study, the aim was to determine the use of premarital carrier screening for SMA in 19,988 people of reproductive age and the incidence of SMA carriers in the population. Methods The research was epidemiological and cross-sectional. The results for people screened from 27 December 2021 to 31 May 2024 were retrospectively assessed. The study received permission from the Clinical Research Ethics Committee. Study population The Premarital National SMA Carrier Screening Program was initiated by the Republic of Turkiye Ministry of Health in December 2021 in all provinces. In this study, the screening results for 19,988 people included in screening from 27 December 2021 to 31 May 2024 in Samsun, Turkiye, were evaluated. Samsun Province contains 17 counties, including 4 central counties. The provincial population is 1,377,546. More than half of this population lives in central counties. The person and their prospective spouse attended their family clinician to obtain a premarital health report or to perform carrier screening and were given information by the family clinician. All participants provided written informed consent. Screening involves a three-stage screening procedure. In the first stage, blood samples are taken from male partners/spouse candidates for screening. Blood samples of 2–3 cc were taken in an EDTA tube, coded with a bar code and entered into the system. If the tubes were not sent to the laboratory on the same day, they were stored at + 4°C in a refrigerator. The tubes are sent to the General Directorate of Public Health Microbiology Reference Laboratories after being placed in suitable boxes to prevent breakage and tested there. If the result is a ‘suspected SMA carrier’, in the second stage, the female partner/spouse candidate is screened. The screening results are communicated to family clinicians through the system, and people may see their results through the Turkish Ministry of Health integrated with the national personal health record system. If both partners/spouse candidates are carriers, in the last stage, couples are referred to a medical genetic expert. They are informed about detailed genetic counseling services, risks and prenatal diagnostic possibilities and are referred accordingly. Quantitative real-time PCR analysis (qRT‒PCR) The Premarital National SMA Carrier Screening Program uses the real-time polymerase chain reaction (real-time PCR/RT‒PCR) method. Real-time quantitative PCR is a simple, rapid and suitable cost method for large-scale routine SMA carrier screening ( 11 ). It is a molecular genetic method with at least 95% sensitivity and specificity for showing copy number changes in the exon 7 and exon 8 regions, especially in the SMN1 gene. Linked to the method, deletion of the SMN1 gene may be missed at rates of 5%, and there may be false-negative results. Data gathering Information such as screening time, age, sex, and address of people participating in the SMA carrier screening was obtained from the Laboratory Information Management System (LIMS). The number of marriages was obtained annually from the Turkish Statistical Institute (TÜİK). Statistical analysis Statistical analysis in the study was performed via SPSS (IBM Statistical Packages for the Social Sciences; Armonk, NY, USA) Version 20.0. The information is presented in tables (Tables 1 – 2 ). The value for statistical significance was accepted as P < 0.05. Categorical data are expressed as numbers (n) and percentages (%). Results From 27 December 2021 to 31 May 2024, a total of 19,988 people participated in premarital national SMA carrier screening (Table 1 ). In 2022, the number of marriages was 9140, with 2306 people participating in screening. For 2022, the uptake rate was determined to be 79.9%. In 2023, the number of marriages was 9058. In 2023, 8698 people participated in screening, and the uptake rate was 96.0%. qPCR was used as a screening method. For the carrier confirmation method, multiplex ligation-dependent probe amplification (MLPA) was used. Among the 19,988 people tested, a total of 453 were suspected to be SMA carriers. This shows that the prevalence of being a carrier was 1:44 (2.26%). Table 2 shows the features of the 453 possible carriers. Of these, 284 were 25–35 years of age (62.7%), and 194 lived in the central counties (42.8%). The 453 healthy SMA carriers with heterozygous deletions in exon 7 of SMN1 were informed about the inheritance and reproductive risk of the disease. They were referred to a genetic clinic for confirmation via the MLPA method and detailed genetic counseling. The spouse candidates for the 453 suspect carriers informed about the disease were called and screened via qPCR. Despite being informed, 12 spouse candidates did not accept screening. Among the 441 SMA carrier spouse candidates, 13 were suspected to be SMA carriers. According to the screening test results for female spouse candidates of carrier males, the carrier prevalence among women was 2.95% (13/441). The confirmation test was performed with MLPA. MLPA testing could not be performed on five couples because they moved out of town or gave up on marriage. In one couple, MLPA could not be confirmed only in the male spouse. Therefore, seven couples were identified as SMA carriers (7/441, 1.59%). These couples were given information about preimplantation genetic diagnosis, and the birth of infants affected by SMA disease was prevented. Table 1 Premarital National SMA Carrier Screening Program Results Variable 2022 2023 2024 (5 months) Total Number of marriages, n 9140 9058 - - Number of people screened, n 7306 8698 3984 19988 Uptake rate, % 79.9 96.0 - - 95% CI, % 79.1–80.7 95.6–96.4 - - Number of carriers (PCR), n 160 217 76 453 Carrier proportion, % 2.19 2.49 1.91 2.27 95% CI, % 1.85–2.53 2.16–2.82 1.48–2.34 2.06–2.48 Partners, n 156 212 73 441 Recall rate, % 97.5 97.7 96.0 97.4 95% CI, % 95.1–99.9 95.7–99.7 91.6-100.4 95.9–98.9 Carrier couples, n 2 3 2 7 Carrier rate of partners, % 1.28 1.42 2.74 1.59 Preimplantation genetic diagnosis, n 1 2 0 3 Table 2 Features of the 453 carriers detected in Samsun Province within the scope of the Premarital National SMA Carrier Screening Program Variable Total(n=) n % 95% CI Age, years 35 71 15.7 12.3–19.1 Residence Central counties 194 42.8 38.2–47.4 Other counties 181 40.0 35.5–44.5 Outside of province 78 17.2 13.7–20.7 Discussion In this study, the aim was to determine the uptake of premarital SMA carrier screening and the frequency of SMA carriers in Samsun, Türkiye. When both parents are SMA carriers, the risk of birthing an infant with SMA disease is 25% for each pregnancy. Among the children born to these couples, 50% are carriers without any disease symptoms, whereas 25% are born healthy and do not carry the disease gene. In our country, premarital SMA carrier screening is available for all couples ( 12 ). In Samsun, from 27 December 2021 to 31 May 2024, 19,988 people were screened. In 2022 and 2023, a total of 18,198 marriages were performed, with a total uptake rate of 87.9% (16004/19198). Broad-scale public screening for SMA carriers of reproductive age in the USA revealed an uptake of 98.7% ( 13 ). A meta-analysis including 169,000 people from 14 different studies revealed that the uptake for prenatal SMA carrier screening was 87–95% in the non-Black population, whereas it was 71% in the Black population ( 14 ). According to the meta-analysis results from Australia in general, there is a strong socioeconomic tendency toward participation in premarital carrier screening. Those living in socioeconomically advantaged postcodes were shown to have a significantly greater probability of participating in premarital carrier screening than those living in more disadvantaged regions did ( 15 ). In our study, the identified uptake pattern was similar to that reported in the literature. These results emphasize the need to consider factors such as sociocultural level, place of residence, educational level and income level among obstacles that may emerge for screening participation. Considering the importance of including the whole population in screening, our results indicate the need to work more carefully with the target population. In our study, the carrier frequency was identified as 1:44. A study of 3049 subjects of reproductive age in China reported that the SMA carrier prevalence was 1:49 (2.03%). In this study, the carrier frequency was 2.3% for women and 1.9% for men, although the difference was not statistically significant ( 16 ). A study including 5200 pregnant patients screened with real-time fluorescence quantitative PCR in China reported that the carrier prevalence was 1.44% (95% confidence interval 1.31–1.65%) ( 17 ). Another study of 13,069 pregnant patients reported a carrier prevalence of 1:56 ( 18 ). In research performed with Asians, differences in SMA carrier rates were found between different ethnic origins. This difference may be due to the sample size, with the frequency of those with 1 SMN1 copy identified as 1.57%. The frequency rose to 4.3% in the Tujia ethnic group ( 4 ). According to the results of a meta-analysis from Australia, the SMA carrier rate was identified as 2% ( 15 ). In the Korean population, the SMA carrier frequency was identified as 1.8% ( 19 ). In our study, screening in women was only performed when a male partner was detected as a carrier. The carrier prevalence in screened female partners was found to be higher than that in men. In Saudi Arabia, a carrier screening study included 4198 participants, 45% of whom were women, and revealed that the carrier prevalence in women (3.7%) was two times greater than that in men (1.6%). The mean carrier prevalence (2.6%) was higher than that reported in other studies. When carriers were questioned about consanguineous marriage, nearly 27% were born via first-degree marriage ( 20 ). In Asian countries where consanguineous marriage is common, the prevalence of SMA is very high ( 21 – 24 ). A study using the MLPA method in Turkiye reported that the consanguineous marriage rate was 33% in patients with homozygote deletion ( 25 ). Families with consanguineous marriages are expected to have increased disease risk in their families for autosomal recessive inherited diseases such as SMA. According to the 2018 Turkey Demographic and Health Survey, the rate of consanguineous marriages in Turkiye is 24% ( 26 ). This situation also supports the relatively high carrier prevalence detected in Turkey. In addition, consanguineous marriage, which is still common in our country, may be the reason for the relatively high carrier prevalence identified in our study. Along with developments in SMA treatment, the importance of neonatal screening and premarital carrier screening has emerged. The national genetic carrier screening program for reproductive health, beginning in 2013 in Israel, reduced the probability of impact from SMA disease by 57% ( 27 ). There are no studies showing the efficacy of screening performed in Turkiye. The data obtained will be beneficial in monitoring rare diseases in the future and in evaluating available programs. It is necessary to develop molecular methodologies for screening rare diseases that may be added to the screening panel and to perform studies to assess the efficacy of screening. It is important to obtain more comprehensive epidemiological data on this topic in Turkiye. The implementation of screening in all family health centers ensures that screening is accessible to the population, which is a very important factor for the success of the program. The optimization of accessibility should be ensured through cooperation with health professionals. Additionally, increasing social awareness about the efficacy of carrier screening is important. Preimplantation genetic testing (PGT) is implemented in 2 centers in our province. The common use of PGT contributes to reducing the incidence of a variety of autosomal recessive diseases. In our country, premarital carrier screening is performed for SMA and hemoglobinopathy. In Turkiye, a country with a high fertility rate among OECD countries, we believe that the expansion of the carrier screening panel is needed because of the high incidence of consanguineous marriage. The target of genetic screening is to allow people to access the most accurate information at the most correct time to ensure that they make knowledgeable decisions. As a result, we believe that it is necessary to perform simultaneous testing for both partners. Limitations One limitation is that, as basic sociodemographic information was not recorded for those participating in screening, possible factors associated with participation in epidemiological screening could not be investigated. Another limitation is that the qPCR test has 95% sensitivity and specificity for copy number variations in the 7th exon of the SMN1 gene; in reality, the carrier prevalence may be greater. Conclusion Our data show that copy number variations in the SNM1 7th exon are not rare in the Turkish population. Considering that 2.26% of the population being SMA carriers is not a proportion that can be ignored, active and effective precautions should be taken to increase the uptake of premarital screening. Additionally, providing genetic counseling as early as possible is important for close monitoring. The obtained data will be beneficial for assessing the efficacy of the current program and assessing aspects that require prioritizing. There is a need for additional studies on this topic. In the literature, the prevalence of SMA in the country in general and its geographical distribution have been weakly defined. We believe that our data will serve as a reference for advanced research in the Turkish population related to the SMA. Declarations Conflict of interest : The authors declare that they have no conflicts of interest related to this article. Funding sources: The authors declare that this study has received no financial support. Ethics Committee Approval: Samsun University Clinical Ethics Boards, 2024/11/8 Author Contributions: Concept: F.N.T.Y., G.K.T Literature Review: F.N.T.Y. Design: F.N.T.Y., G.K.T. Data acquisition: G.K.T Analysis and interpretation: F.N.T.Y., G.K.T Writing the manuscript: F.N.T.Y. Critical revision of manuscript: F.N.T.Y., G.K.T Acknowledgments We thank Catherine Yiğit for English editing of this manuscript. References Verhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review. Orphanet J Rare Dis. 2017 ; 12(1): 124. doi: 10.1186/s13023-017-0671-8. PMID: 28676062; PMCID: PMC5496354. Monani UR. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron. 2005; 48: 885–96. Ogino S, Wilson RB, Gold B. New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations. Eur J Hum Genet . 2004; 12(12): 1015-1023. doi:10.1038/sj.ejhg.5201288 Sugarman EA, et al. Panethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012; 20(1): 27–32. Türkiye Cumhuriyeti Sağlık Bakanlığı. Evlilik Öncesi Spinal Musküler Atrofi (SMA) Taşıyıcı Tarama Programı. https://hsgm.saglik.gov.tr/tr/tarama-programlari/evlilik-oncesi-sma-tasiyici-tarama-programi.html (accessed Jan 17, 2024). (in Turkish) Kolb SJ, Kissel JT. Spinal muscular atrophy: a timely review. Arch Neurol. 2011; 68(8): 979–984. Finkel RS, Chiriboga CA, Vajsar J et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016; 388: 3017–3026. Arnold ES, Fischbeck KH. Spinal muscular atrophy. Handb Clin Neurol 2018;148:591-601. Therrell BL, Padilla CD, Borrajo GJC, Khneisser I, Schielen PCJI, Knight-Madden J, Malherbe HL, Kase M. Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020-2023). Int J Neonatal Screen. 2024 May 23;10(2):38. doi: 10.3390/ijns10020038. De Siqueira Carvalho AA, Tychon C, Servais L. Newborn screening for spinal muscular atrophy - what have we learned? Expert Rev Neurother. 2023; 23(11): 1005-1012. doi: 10.1080/14737175.2023.2252179. Epub 2023 Aug 30. PMID: 37635694. Gülşen M, Ceylan AC, Bahsi T, Çubukçu HC, Dursun OB. Validation of SMA screening kits with SMN1 gene analysis in a Turkish cohort. Clin Chim Acta. 2024; 555: 117793. doi: 10.1016/j.cca.2024.117793. Epub 2024 Feb 2. PMID: 38309554. Republic of Turkey Ministry of Health. Spinal muscular atrophy carrier screening program field guide. Republic of Turkey Ministry of Health. General Directorate of Public Health (2023). https://hsgm.saglik.gov.tr/depo/birimler/cocuk-ergen-sagligi-db/Programlar/EO_SMA_TASIYICI_TARAMA_PROGRAMI_SAHA_REHBERI.pdf (accessed December 28, 2024) Prior TW, Snyder PJ, Rink BD, et al. Newborn and carrier screening for spinal muscular atrophy. Am J Med Genet A . 2010; 152A(7): 1608-1616. doi:10.1002/ajmg.a.33474 MacDonald WK, Hamilton D, Kuhle S. SMA carrier testing: a metaanalysis of differences in test performance by ethnic group. Prenat Diagn. 2014; 34: 1219–1226. Robson SJ, Caramins M, Saad M, Suthers G. Socioeconomic status and uptake of reproductive carrier screening in Australia. Aust N Z J Obstet Gynecol. 2020; 60(6): 976-979. doi: 10.1111/ajo.13206. Epub 2020 Aug 4. PMID: 32748403. Zhang Y, Wang L, He J, Guo J, Jin C, Tang X et al. Result of carrier screening for spinal muscular atrophy among 3049 reproductive-age individuals from Yunnan region. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020; 37(4): 384-388. Chinese. doi: 10.3760/cma.j.issn.1003-9406.2020.04.005. PMID: 32219818. Huang Z, Yang Q, Ye J, Huang J, Lin J, Chen J et al. Screening and prenatal diagnosis of survival motor neuron gene deletion in pregnant women in Zhaoqing city, Guangdong Province. BMC Med Genomics. 2023; 16(1): 39. doi: 10.1186/s12920-023-01468-0. PMID: 36859245; PMCID: PMC9976494. Zhang J, Wang Y, Ma D et al. Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in 13,069 Chinese Pregnant Women. J Mol Diagn . 2020; 22(6): 817-822. doi:10.1016/j.jmoldx.2020.03.001 Park JE, Yun SA, Roh EY, Yoon JH, Shin S, Ki CS. Carrier Frequency of Spinal Muscular Atrophy in a Large-scale Korean Population. Ann Lab Med . 2020; 40(4): 326-330. doi:10.3343/alm.2020.40.4.326 Al Jumah M, Al Rajeh S, Eyaid W, Al-Jedai A, Al Mudaiheem H, Al Shehri A et al. Spinal muscular atrophy carrier frequency in Saudi Arabia. Mol Genet Genomic Med. 2022; 10(11): e2049. doi: 10.1002/mgg3.2049. Epub 2022 Sep 5. PMID: 36062320; PMCID: PMC9651606. Ibrahim S, Moatter T, Saleem AF. Spinal muscular atrophy: clinical spectrum and genetic mutations in Pakistani children. Neurol India . 2012 ;60(3): 294-298. doi:10.4103/0028-3886.98514 Tunçbílek E, Koc I. Consanguineous marriage in Turkey and its impact on fertility and mortality. Ann Hum Genet. 1994 Oct;58(4):321-9. doi: 10.1111/j.1469-1809.1994.tb00729.x. PMID: 7864588. Modell B, Darr A. Science and society: genetic counseling and customary consanguineous marriage. Nat Rev Genet. 2002 Mar;3(3):225-9. doi: 10.1038/nrg754. PMID: 11972160. Mansouri V, Heidari M, Bemanalizadeh M, Azizimalamiri R, Nafissi S, Akbari MG, Barzegar M, Moayedi AR, Badv RS, Mohamadi M, Tavasoli AR, Amirsalari S, Khajeh A, Inaloo S, Fatehi F, Hosseinpour S, Babaei M, Hosseini SA, Mahdi Hosseiny SM, Fayyazi A, Hosseini F, Toosi MB, Khosroshahi N, Ghabeli H, Biglari HN, Kakhki SK, Mirlohi SH, Bidabadi E, Mohammadi B, Omrani A, Sedighi M, Vafaee-Shahi M, Rasulinezhad M, Hoseini SM, Movahedinia M, Rezaei Z, Karimi P, Farshadmoghadam H, Anvari S, Yaghini O, Nasiri J, Zamani G, Ashrafi MR. The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy. J Neuromuscul Dis. 2023;10(2):211-225. doi: 10.3233/JND-221614. PMID: 36776076. Arikan Y, Berker Karauzum S, Uysal H, Mihci E, Nur B, Duman O et al. Evaluation of exonic copy numbers of SMN1 and SMN2 genes in SMA. Gene. 2022; 823: 146322. doi: 10.1016/j.gene.2022.146322. Epub 2022 Feb 25. PMID: 35219815. Koç İ (2022) Türkiye’de Akraba evliliklerinin yaygınlığının değişimi ve dirençli grupların belirlenmesi: 2018 Türkiye Nüfus ve Sağlık Araştırması’ndan evlilik kuşaklarına göre analizler. Turkish J Public Health 20(3):423–438 Singer A, Sagi-Dain L. Impact of a national genetic carrier-screening program for reproductive purposes. Acta Obstet Gynecol Scand. 2020; 99(6): 802-808. doi: 10.1111/aogs.13858. Epub 2020 Apr 13. PMID: 32242916. Additional Declarations The authors declare no competing interests. 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5908427","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":407356509,"identity":"af3b7e69-610d-4d08-b5ff-526e64a65401","order_by":0,"name":"Feyza Nur Topcu Yenercag","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYBAC9gYILWcApgwsCGvhOcAMpo0NGEAMAwnitSRuAGthIEaLdP/BxwU1h9O3s/cf3fCjQIKBv707Ab8WmcPMxjOOHc7d2XOY7WYP0GESZ85uwKvFXiKZTZq34XDuhhvJbDd4gFoMJHLxa+GBakk3AGq5+YcULQkgLbeJtcUY6Jd0ww1nDpvdljGQ4CHoFx6JxIfAELOWNzje+Ozmmz82cvztvfi1gAAzihkElWNoGQWjYBSMglGAAQB6jEFu143ucgAAAABJRU5ErkJggg==","orcid":"","institution":"Provincial Health Directorate, Samsun, Turkiye","correspondingAuthor":true,"prefix":"","firstName":"Feyza","middleName":"Nur Topcu","lastName":"Yenercag","suffix":""},{"id":407356510,"identity":"9db2eef8-4423-4148-ba4a-2b94ecd5be51","order_by":1,"name":"Günay Kaya Tarhan","email":"","orcid":"","institution":"Provincial Health Directorate, Samsun, Turkiye","correspondingAuthor":false,"prefix":"","firstName":"Günay","middleName":"Kaya","lastName":"Tarhan","suffix":""}],"badges":[],"createdAt":"2025-01-26 22:13:50","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5908427/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5908427/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74930162,"identity":"2f922db8-00cf-4019-89fd-512bcc74ade8","added_by":"auto","created_at":"2025-01-28 12:09:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":504522,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5908427/v1/1693ed92-b1ec-4fe1-8313-d09eb5d5418d.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003ePremarital spinal muscular atrophy screening program results from a province in the Black Sea region of Turkiye: Two years of experience\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSpinal muscular atrophy (SMA) is a neuromuscular disease that is one of the most common genetic causes of infant mortality worldwide. Additionally, it is the second most common and deadly autosomal recessive disease (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). SMA frequently occurs with homozygotic deletion or mutation of the survival motor neuron (SMN) gene located on the 5th chromosome. If the SMN protein cannot be produced at adequate levels, degeneration of alpha motor neurons occurs, and atrophy develops in muscles (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The most frequent mutation occurring in the SMN1 gene is deletion of exon 7, which is located on the 5th chromosome (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSMA is frequently diagnosed late after symptoms appear, as it is a rare disease with heterogeneous findings. According to the results of a systematic review, the incidence of SMA worldwide is 10 per 100,000 live births. The prevalence was determined to be 1\u0026ndash;3 per 100,000 people, with low detection rates thought to be related to the shortened life expectancy to a great degree (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). According to a multinational study investigating different ethnic groups, the SMA carrier frequency varies from 1:47\u0026ndash;72 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn Turkiye, the incidence of SMA and carrier rates are not clearly known. However, it is thought that our country, with frequent consanguineous marriages, has high rates of autosomal recessive heritable diseases and carrier rates. Considering that nearly 1,100,000 live births have occurred per year in recent years, the annual new case number is predicted to range from 130\u0026ndash;180 (mean: 150). Nearly 3000 SMA patients are monitored (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe SMA is divided into 4 subtypes according to age at onset and severity of muscle weakness. SMA type 1 (Werdnig\u0026ndash;Hoffman disease) is the earliest and most severe form, causing severe and progressive respiratory problems and hypotonia in the first 6 months of life. SMA type 2 (subacute form) generally begin at 6\u0026ndash;18 months, with symptoms similar to those of type 1, although they do not worsen rapidly. SMA type 3 (Kugelberg\u0026ndash;Welander disease) begins after the age of 2 years, and the first symptom is difficulty walking. Type 4 begins in adulthood and is the mildest form.\u003c/p\u003e \u003cp\u003ePotential treatment approaches have been developed with the understanding that SMA disease has molecular genetic features (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Two treatment methods (nusinersen and zolgensma) have received FDA approval and significantly increase quality of life in the long term (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Therapeutic approaches are known to increase the level of SMN in motor neurons when applied presymptomatically. Therefore, early diagnosis and treatment can slow the neurodegenerative process (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFor genetic diseases, primary (screening of society for carriers, screening of populations at risk, premarital screening programs, preconception screening), secondary (neonatal screening programs (NSP), treatment of presymptomatic infants) and tertiary (treatment of symptomatic infants) protection are available. Owing to NSP, SMA disease is detected in the early period, and severe forms may be prevented with presymptomatic treatment. Health economy studies revealed that although the value of NSP was clearly revealed, a problem frequently reported in upper middle-income countries is the formation of a greater patient burden than the system can treat (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This increases the importance of premarital screening (PMS), which prevents the birth of sick infants (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). A premarital SMA screening program is implemented throughout Turkiye. The aim of the program is to offer genetic counseling and prenatal or preimplantation diagnostic test options to couples identified as carriers. Additionally, the long-term target is to reduce morbidity and mortality associated with SMA (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, the aim was to determine the use of premarital carrier screening for SMA in 19,988 people of reproductive age and the incidence of SMA carriers in the population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe research was epidemiological and cross-sectional. The results for people screened from 27 December 2021 to 31 May 2024 were retrospectively assessed. The study received permission from the Clinical Research Ethics Committee.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThe Premarital National SMA Carrier Screening Program was initiated by the Republic of Turkiye Ministry of Health in December 2021 in all provinces. In this study, the screening results for 19,988 people included in screening from 27 December 2021 to 31 May 2024 in Samsun, Turkiye, were evaluated. Samsun Province contains 17 counties, including 4 central counties. The provincial population is 1,377,546. More than half of this population lives in central counties. The person and their prospective spouse attended their family clinician to obtain a premarital health report or to perform carrier screening and were given information by the family clinician. All participants provided written informed consent. Screening involves a three-stage screening procedure. In the first stage, blood samples are taken from male partners/spouse candidates for screening. Blood samples of 2\u0026ndash;3 cc were taken in an EDTA tube, coded with a bar code and entered into the system. If the tubes were not sent to the laboratory on the same day, they were stored at +\u0026thinsp;4\u0026deg;C in a refrigerator. The tubes are sent to the General Directorate of Public Health Microbiology Reference Laboratories after being placed in suitable boxes to prevent breakage and tested there. If the result is a \u0026lsquo;suspected SMA carrier\u0026rsquo;, in the second stage, the female partner/spouse candidate is screened. The screening results are communicated to family clinicians through the system, and people may see their results through the Turkish Ministry of Health integrated with the national personal health record system. If both partners/spouse candidates are carriers, in the last stage, couples are referred to a medical genetic expert. They are informed about detailed genetic counseling services, risks and prenatal diagnostic possibilities and are referred accordingly.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eQuantitative real-time PCR analysis (qRT‒PCR)\u003c/h3\u003e\n\u003cp\u003eThe Premarital National SMA Carrier Screening Program uses the real-time polymerase chain reaction (real-time PCR/RT‒PCR) method. Real-time quantitative PCR is a simple, rapid and suitable cost method for large-scale routine SMA carrier screening (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). It is a molecular genetic method with at least 95% sensitivity and specificity for showing copy number changes in the exon 7 and exon 8 regions, especially in the SMN1 gene. Linked to the method, deletion of the SMN1 gene may be missed at rates of 5%, and there may be false-negative results.\u003c/p\u003e\n\u003ch3\u003eData gathering\u003c/h3\u003e\n\u003cp\u003eInformation such as screening time, age, sex, and address of people participating in the SMA carrier screening was obtained from the Laboratory Information Management System (LIMS). The number of marriages was obtained annually from the Turkish Statistical Institute (T\u0026Uuml;İK).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis in the study was performed via SPSS (IBM Statistical Packages for the Social Sciences; Armonk, NY, USA) Version 20.0. The information is presented in tables (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The value for statistical significance was accepted as P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Categorical data are expressed as numbers (n) and percentages (%).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFrom 27 December 2021 to 31 May 2024, a total of 19,988 people participated in premarital national SMA carrier screening (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In 2022, the number of marriages was 9140, with 2306 people participating in screening. For 2022, the uptake rate was determined to be 79.9%. In 2023, the number of marriages was 9058. In 2023, 8698 people participated in screening, and the uptake rate was 96.0%. qPCR was used as a screening method. For the carrier confirmation method, multiplex ligation-dependent probe amplification (MLPA) was used. Among the 19,988 people tested, a total of 453 were suspected to be SMA carriers. This shows that the prevalence of being a carrier was 1:44 (2.26%). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the features of the 453 possible carriers. Of these, 284 were 25\u0026ndash;35 years of age (62.7%), and 194 lived in the central counties (42.8%). The 453 healthy SMA carriers with heterozygous deletions in exon 7 of SMN1 were informed about the inheritance and reproductive risk of the disease. They were referred to a genetic clinic for confirmation via the MLPA method and detailed genetic counseling. The spouse candidates for the 453 suspect carriers informed about the disease were called and screened via qPCR. Despite being informed, 12 spouse candidates did not accept screening. Among the 441 SMA carrier spouse candidates, 13 were suspected to be SMA carriers. According to the screening test results for female spouse candidates of carrier males, the carrier prevalence among women was 2.95% (13/441). The confirmation test was performed with MLPA. MLPA testing could not be performed on five couples because they moved out of town or gave up on marriage. In one couple, MLPA could not be confirmed only in the male spouse. Therefore, seven couples were identified as SMA carriers (7/441, 1.59%). These couples were given information about preimplantation genetic diagnosis, and the birth of infants affected by SMA disease was prevented.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePremarital National SMA Carrier Screening Program Results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2022\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2024 (5 months)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of marriages, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of people screened, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8698\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3984\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19988\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUptake rate, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e95% CI, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.1\u0026ndash;80.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.6\u0026ndash;96.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of carriers (PCR), n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e453\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarrier proportion, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e95% CI, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.85\u0026ndash;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.16\u0026ndash;2.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.48\u0026ndash;2.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.06\u0026ndash;2.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartners, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e441\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecall rate, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e97.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e95% CI, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.1\u0026ndash;99.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.7\u0026ndash;99.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91.6-100.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95.9\u0026ndash;98.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarrier couples, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCarrier rate of partners, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreimplantation genetic diagnosis, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFeatures of the 453 carriers detected in Samsun Province within the scope of the Premarital National SMA Carrier Screening Program\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eTotal(n=)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.8\u0026ndash;25.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u0026ndash;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e284\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.2\u0026ndash;67.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.3\u0026ndash;19.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResidence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral counties\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.2\u0026ndash;47.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther counties\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.5\u0026ndash;44.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutside of province\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.7\u0026ndash;20.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the aim was to determine the uptake of premarital SMA carrier screening and the frequency of SMA carriers in Samsun, T\u0026uuml;rkiye. When both parents are SMA carriers, the risk of birthing an infant with SMA disease is 25% for each pregnancy. Among the children born to these couples, 50% are carriers without any disease symptoms, whereas 25% are born healthy and do not carry the disease gene. In our country, premarital SMA carrier screening is available for all couples (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In Samsun, from 27 December 2021 to 31 May 2024, 19,988 people were screened. In 2022 and 2023, a total of 18,198 marriages were performed, with a total uptake rate of 87.9% (16004/19198).\u003c/p\u003e \u003cp\u003eBroad-scale public screening for SMA carriers of reproductive age in the USA revealed an uptake of 98.7% (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). A meta-analysis including 169,000 people from 14 different studies revealed that the uptake for prenatal SMA carrier screening was 87\u0026ndash;95% in the non-Black population, whereas it was 71% in the Black population (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). According to the meta-analysis results from Australia in general, there is a strong socioeconomic tendency toward participation in premarital carrier screening. Those living in socioeconomically advantaged postcodes were shown to have a significantly greater probability of participating in premarital carrier screening than those living in more disadvantaged regions did (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In our study, the identified uptake pattern was similar to that reported in the literature. These results emphasize the need to consider factors such as sociocultural level, place of residence, educational level and income level among obstacles that may emerge for screening participation. Considering the importance of including the whole population in screening, our results indicate the need to work more carefully with the target population.\u003c/p\u003e \u003cp\u003eIn our study, the carrier frequency was identified as 1:44. A study of 3049 subjects of reproductive age in China reported that the SMA carrier prevalence was 1:49 (2.03%). In this study, the carrier frequency was 2.3% for women and 1.9% for men, although the difference was not statistically significant (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). A study including 5200 pregnant patients screened with real-time fluorescence quantitative PCR in China reported that the carrier prevalence was 1.44% (95% confidence interval 1.31\u0026ndash;1.65%) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Another study of 13,069 pregnant patients reported a carrier prevalence of 1:56 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In research performed with Asians, differences in SMA carrier rates were found between different ethnic origins. This difference may be due to the sample size, with the frequency of those with 1 SMN1 copy identified as 1.57%. The frequency rose to 4.3% in the Tujia ethnic group (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). According to the results of a meta-analysis from Australia, the SMA carrier rate was identified as 2% (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In the Korean population, the SMA carrier frequency was identified as 1.8% (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, screening in women was only performed when a male partner was detected as a carrier. The carrier prevalence in screened female partners was found to be higher than that in men. In Saudi Arabia, a carrier screening study included 4198 participants, 45% of whom were women, and revealed that the carrier prevalence in women (3.7%) was two times greater than that in men (1.6%). The mean carrier prevalence (2.6%) was higher than that reported in other studies. When carriers were questioned about consanguineous marriage, nearly 27% were born via first-degree marriage (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In Asian countries where consanguineous marriage is common, the prevalence of SMA is very high (\u003cspan additionalcitationids=\"CR22 CR23\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). A study using the MLPA method in Turkiye reported that the consanguineous marriage rate was 33% in patients with homozygote deletion (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Families with consanguineous marriages are expected to have increased disease risk in their families for autosomal recessive inherited diseases such as SMA. According to the 2018 Turkey Demographic and Health Survey, the rate of consanguineous marriages in Turkiye is 24% (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). This situation also supports the relatively high carrier prevalence detected in Turkey. In addition, consanguineous marriage, which is still common in our country, may be the reason for the relatively high carrier prevalence identified in our study.\u003c/p\u003e \u003cp\u003eAlong with developments in SMA treatment, the importance of neonatal screening and premarital carrier screening has emerged. The national genetic carrier screening program for reproductive health, beginning in 2013 in Israel, reduced the probability of impact from SMA disease by 57% (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). There are no studies showing the efficacy of screening performed in Turkiye. The data obtained will be beneficial in monitoring rare diseases in the future and in evaluating available programs. It is necessary to develop molecular methodologies for screening rare diseases that may be added to the screening panel and to perform studies to assess the efficacy of screening. It is important to obtain more comprehensive epidemiological data on this topic in Turkiye.\u003c/p\u003e \u003cp\u003eThe implementation of screening in all family health centers ensures that screening is accessible to the population, which is a very important factor for the success of the program. The optimization of accessibility should be ensured through cooperation with health professionals. Additionally, increasing social awareness about the efficacy of carrier screening is important. Preimplantation genetic testing (PGT) is implemented in 2 centers in our province. The common use of PGT contributes to reducing the incidence of a variety of autosomal recessive diseases.\u003c/p\u003e \u003cp\u003eIn our country, premarital carrier screening is performed for SMA and hemoglobinopathy. In Turkiye, a country with a high fertility rate among OECD countries, we believe that the expansion of the carrier screening panel is needed because of the high incidence of consanguineous marriage. The target of genetic screening is to allow people to access the most accurate information at the most correct time to ensure that they make knowledgeable decisions. As a result, we believe that it is necessary to perform simultaneous testing for both partners.\u003c/p\u003e\n\u003ch3\u003eLimitations\u003c/h3\u003e\n\u003cp\u003eOne limitation is that, as basic sociodemographic information was not recorded for those participating in screening, possible factors associated with participation in epidemiological screening could not be investigated. Another limitation is that the qPCR test has 95% sensitivity and specificity for copy number variations in the 7th exon of the SMN1 gene; in reality, the carrier prevalence may be greater.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur data show that copy number variations in the SNM1 7th exon are not rare in the Turkish population. Considering that 2.26% of the population being SMA carriers is not a proportion that can be ignored, active and effective precautions should be taken to increase the uptake of premarital screening. Additionally, providing genetic counseling as early as possible is important for close monitoring. The obtained data will be beneficial for assessing the efficacy of the current program and assessing aspects that require prioritizing. There is a need for additional studies on this topic. In the literature, the prevalence of SMA in the country in general and its geographical distribution have been weakly defined. We believe that our data will serve as a reference for advanced research in the Turkish population related to the SMA.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003einterest\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare\u0026nbsp;that they have no conflicts\u0026nbsp;of interest related to this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding sources:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that this\u0026nbsp;study has received no financial support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Committee Approval:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSamsun University Clinical Ethics Boards, 2024/11/8\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept: F.N.T.Y., G.K.T\u003c/p\u003e\n\u003cp\u003eLiterature Review: F.N.T.Y.\u003c/p\u003e\n\u003cp\u003eDesign: F.N.T.Y., G.K.T.\u003c/p\u003e\n\u003cp\u003eData acquisition: G.K.T\u003c/p\u003e\n\u003cp\u003eAnalysis and interpretation: F.N.T.Y., G.K.T\u003c/p\u003e\n\u003cp\u003eWriting\u0026nbsp;the\u0026nbsp;manuscript: F.N.T.Y.\u003c/p\u003e\n\u003cp\u003eCritical revision of manuscript: F.N.T.Y., G.K.T\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Catherine Yiğit for English editing of this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVerhaart IEC, Robertson A, Wilson IJ, Aartsma-Rus A, Cameron S, Jones CC et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review. Orphanet J Rare Dis. 2017 ; 12(1): 124. doi: 10.1186/s13023-017-0671-8. PMID: 28676062; PMCID: PMC5496354.\u003c/li\u003e\n\u003cli\u003eMonani UR. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron. 2005; 48: 885\u0026ndash;96.\u003c/li\u003e\n\u003cli\u003eOgino S, Wilson RB, Gold B. New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations. \u003cem\u003eEur J Hum Genet\u003c/em\u003e. 2004; 12(12): 1015-1023. doi:10.1038/sj.ejhg.5201288\u003c/li\u003e\n\u003cli\u003eSugarman EA, et al. Panethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of \u0026gt;72,400 specimens. Eur J Hum Genet. 2012; 20(1): 27\u0026ndash;32.\u003c/li\u003e\n\u003cli\u003eT\u0026uuml;rkiye Cumhuriyeti Sağlık Bakanlığı. Evlilik \u0026Ouml;ncesi Spinal Musk\u0026uuml;ler Atrofi (SMA) Taşıyıcı Tarama Programı. https://hsgm.saglik.gov.tr/tr/tarama-programlari/evlilik-oncesi-sma-tasiyici-tarama-programi.html (accessed Jan 17, 2024). (in Turkish)\u003c/li\u003e\n\u003cli\u003eKolb SJ, Kissel JT. Spinal muscular atrophy: a timely review. Arch Neurol. 2011; 68(8): 979\u0026ndash;984.\u003c/li\u003e\n\u003cli\u003eFinkel RS, Chiriboga CA, Vajsar J et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016; 388: 3017\u0026ndash;3026.\u003c/li\u003e\n\u003cli\u003eArnold ES, Fischbeck KH. Spinal muscular atrophy. Handb Clin Neurol 2018;148:591-601.\u003c/li\u003e\n\u003cli\u003eTherrell BL, Padilla CD, Borrajo GJC, Khneisser I, Schielen PCJI, Knight-Madden J, Malherbe HL, Kase M. Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020-2023). Int J Neonatal Screen. 2024 May 23;10(2):38. doi: 10.3390/ijns10020038.\u003c/li\u003e\n\u003cli\u003eDe Siqueira Carvalho AA, Tychon C, Servais L. Newborn screening for spinal muscular atrophy - what have we learned? Expert Rev Neurother. 2023; 23(11): 1005-1012. doi: 10.1080/14737175.2023.2252179. Epub 2023 Aug 30. PMID: 37635694.\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;lşen M, Ceylan AC, Bahsi T, \u0026Ccedil;ubuk\u0026ccedil;u HC, Dursun OB. Validation of SMA screening kits with SMN1 gene analysis in a Turkish cohort. Clin Chim Acta. 2024; 555: 117793. doi: 10.1016/j.cca.2024.117793. Epub 2024 Feb 2. PMID: 38309554.\u003c/li\u003e\n\u003cli\u003eRepublic of Turkey Ministry of Health. Spinal muscular atrophy carrier screening program field guide. Republic of Turkey Ministry of Health. General Directorate of Public Health (2023). https://hsgm.saglik.gov.tr/depo/birimler/cocuk-ergen-sagligi-db/Programlar/EO_SMA_TASIYICI_TARAMA_PROGRAMI_SAHA_REHBERI.pdf (accessed December 28, 2024)\u003c/li\u003e\n\u003cli\u003ePrior TW, Snyder PJ, Rink BD, et al. Newborn and carrier screening for spinal muscular atrophy. \u003cem\u003eAm J Med Genet A\u003c/em\u003e. 2010; 152A(7): 1608-1616. doi:10.1002/ajmg.a.33474\u003c/li\u003e\n\u003cli\u003eMacDonald WK, Hamilton D, Kuhle S. SMA carrier testing: a metaanalysis of differences in test performance by ethnic group. Prenat Diagn. 2014; 34: 1219\u0026ndash;1226.\u003c/li\u003e\n\u003cli\u003eRobson SJ, Caramins M, Saad M, Suthers G. Socioeconomic status and uptake of reproductive carrier screening in Australia. Aust N Z J Obstet Gynecol. 2020; 60(6): 976-979. doi: 10.1111/ajo.13206. Epub 2020 Aug 4. PMID: 32748403.\u003c/li\u003e\n\u003cli\u003eZhang Y, Wang L, He J, Guo J, Jin C, Tang X et al. Result of carrier screening for spinal muscular atrophy among 3049 reproductive-age individuals from Yunnan region. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020; 37(4): 384-388. Chinese. doi: 10.3760/cma.j.issn.1003-9406.2020.04.005. PMID: 32219818.\u003c/li\u003e\n\u003cli\u003eHuang Z, Yang Q, Ye J, Huang J, Lin J, Chen J et al. Screening and prenatal diagnosis of survival motor neuron gene deletion in pregnant women in Zhaoqing city, Guangdong Province. BMC Med Genomics. 2023; 16(1): 39. doi: 10.1186/s12920-023-01468-0. PMID: 36859245; PMCID: PMC9976494.\u003c/li\u003e\n\u003cli\u003eZhang J, Wang Y, Ma D et al. Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in 13,069 Chinese Pregnant Women. \u003cem\u003eJ Mol Diagn\u003c/em\u003e. 2020; 22(6): 817-822. doi:10.1016/j.jmoldx.2020.03.001\u003c/li\u003e\n\u003cli\u003ePark JE, Yun SA, Roh EY, Yoon JH, Shin S, Ki CS. Carrier Frequency of Spinal Muscular Atrophy in a Large-scale Korean Population. \u003cem\u003eAnn Lab Med\u003c/em\u003e. 2020; 40(4): 326-330. doi:10.3343/alm.2020.40.4.326\u003c/li\u003e\n\u003cli\u003eAl Jumah M, Al Rajeh S, Eyaid W, Al-Jedai A, Al Mudaiheem H, Al Shehri A et al. Spinal muscular atrophy carrier frequency in Saudi Arabia. Mol Genet Genomic Med. 2022; 10(11): e2049. doi: 10.1002/mgg3.2049. Epub 2022 Sep 5. PMID: 36062320; PMCID: PMC9651606.\u003c/li\u003e\n\u003cli\u003eIbrahim S, Moatter T, Saleem AF. Spinal muscular atrophy: clinical spectrum and genetic mutations in Pakistani children. \u003cem\u003eNeurol India\u003c/em\u003e. 2012 ;60(3): 294-298. doi:10.4103/0028-3886.98514\u003c/li\u003e\n\u003cli\u003eTun\u0026ccedil;b\u0026iacute;lek E, Koc I. Consanguineous marriage in Turkey and its impact on fertility and mortality. Ann Hum Genet. 1994 Oct;58(4):321-9. doi: 10.1111/j.1469-1809.1994.tb00729.x. PMID: 7864588.\u003c/li\u003e\n\u003cli\u003eModell B, Darr A. Science and society: genetic counseling and customary consanguineous marriage. Nat Rev Genet. 2002 Mar;3(3):225-9. doi: 10.1038/nrg754. PMID: 11972160.\u003c/li\u003e\n\u003cli\u003eMansouri V, Heidari M, Bemanalizadeh M, Azizimalamiri R, Nafissi S, Akbari MG, Barzegar M, Moayedi AR, Badv RS, Mohamadi M, Tavasoli AR, Amirsalari S, Khajeh A, Inaloo S, Fatehi F, Hosseinpour S, Babaei M, Hosseini SA, Mahdi Hosseiny SM, Fayyazi A, Hosseini F, Toosi MB, Khosroshahi N, Ghabeli H, Biglari HN, Kakhki SK, Mirlohi SH, Bidabadi E, Mohammadi B, Omrani A, Sedighi M, Vafaee-Shahi M, Rasulinezhad M, Hoseini SM, Movahedinia M, Rezaei Z, Karimi P, Farshadmoghadam H, Anvari S, Yaghini O, Nasiri J, Zamani G, Ashrafi MR. The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy. J Neuromuscul Dis. 2023;10(2):211-225. doi: 10.3233/JND-221614. PMID: 36776076.\u003c/li\u003e\n\u003cli\u003eArikan Y, Berker Karauzum S, Uysal H, Mihci E, Nur B, Duman O et al. Evaluation of exonic copy numbers of SMN1 and SMN2 genes in SMA. Gene. 2022; 823: 146322. doi: 10.1016/j.gene.2022.146322. Epub 2022 Feb 25. PMID: 35219815.\u003c/li\u003e\n\u003cli\u003eKo\u0026ccedil; İ (2022) T\u0026uuml;rkiye\u0026rsquo;de Akraba evliliklerinin yaygınlığının değişimi ve diren\u0026ccedil;li grupların belirlenmesi: 2018 T\u0026uuml;rkiye N\u0026uuml;fus ve Sağlık Araştırması\u0026rsquo;ndan evlilik kuşaklarına g\u0026ouml;re analizler. Turkish J Public Health 20(3):423\u0026ndash;438\u003c/li\u003e\n\u003cli\u003eSinger A, Sagi-Dain L. Impact of a national genetic carrier-screening program for reproductive purposes. Acta Obstet Gynecol Scand. 2020; 99(6): 802-808. doi: 10.1111/aogs.13858. Epub 2020 Apr 13. PMID: 32242916.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Provincial Health Directorate, Samsun, Turkiye","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Spinal muscular atrophy, Prenatal diagnosis, Carrier screening, SMN1","lastPublishedDoi":"10.21203/rs.3.rs-5908427/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5908427/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eSpinal muscular atrophy (SMA) is a life-shortening autosomal recessive neuromuscular disease. In this study, the aim was to determine the use of premarital SMA carrier screening and the frequency of SMA carriers in this population.\u003c/p\u003e\u003ch2\u003eStudy Design:\u003c/h2\u003e \u003cp\u003eThe Premarital National SMA Carrier Screening Program was applied to 19,988 people between 27 December 2021 and 31 May 2024.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eA total of 453 people were found to be SMA carriers with heterozygote deletions in exon 7 of SMN1, indicating a carrier prevalence of approximately 1:44 (2.26%) in the population. After detailed genetic counseling, 441 partners were tested, and 13 were identified as SMA carriers. These couples were given information about preimplantation genetic diagnosis, and the birth of infants affected by SMA disease was prevented.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn our experience with carrier screening, awareness of premarital SMA carrier screening can be effectively maximized.\u003c/p\u003e","manuscriptTitle":"Premarital spinal muscular atrophy screening program results from a province in the Black Sea region of Turkiye: Two years of experience","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-28 12:01:30","doi":"10.21203/rs.3.rs-5908427/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dc4c7a9f-392f-47a8-ab18-da9c81304af1","owner":[],"postedDate":"January 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":43435430,"name":"Medical Genetics"}],"tags":[],"updatedAt":"2025-01-28T12:01:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-28 12:01:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5908427","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5908427","identity":"rs-5908427","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}