{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:56:10Z","timestamp":1791046570461,"version":"4.1.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T00:00:00Z","timestamp":1727568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"\u201c139\u201d Training Program for High Level Medical Talents in Guangxi","award":["No. G201903017"],"award-info":[{"award-number":["No. G201903017"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genomics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Spinal muscular atrophy (SMA) is the second most common fatal genetic disease in infancy. It is caused by deletion or intragenic pathogenic variants of the causative gene\n                    <jats:italic>SMN1<\/jats:italic>\n                    , which degenerates anterior horn motor neurons and leads to progressive myasthenia and muscle atrophy. Early treatment improves motor function and prognosis in patients with SMA, but drugs are expensive and do not cure the disease. Therefore, carrier screening seems to be the most effective way to prevent SMA birth defects. In this study, we genetically analyzed 1400 samples using multiplex ligation-dependent probe amplification (MLPA) and quantitative polymerase chain reaction (qPCR), and compared the consistency of the results. We randomly selected 44 samples with consistent MLPA and qPCR results for comprehensive SMA analysis (CASMA) using a long-read sequencing (LRS)-based approach. CASMA results showed 100% consistency, visually and intuitively explained the inconsistency between exons 7 and 8 copy numbers detected by MLPA in 13 samples. A total of 16 samples showed inconsistent MLPA and qPCR results for\n                    <jats:italic>SMN1<\/jats:italic>\n                    exon 7. CASMA was performed on all samples and the results were consistent with those of resampling for MLPA and qPCR detection. CASMA also detected an additional intragenic variant c.-39A&gt;G in a sample with two copies of\n                    <jats:italic>SMN1<\/jats:italic>\n                    (RT02). Finally, we detected 23 SMA carriers, with an estimated carrier rate of 1\/61 in this cohort. In addition, CASMA identified the \u201c2\u2009+\u20090\u201d carrier status of\n                    <jats:italic>SMN1<\/jats:italic>\n                    and\n                    <jats:italic>SMN2<\/jats:italic>\n                    in a family by analyzing the genotypes of only three samples (parents and one sibling). CASMA has great advantages over MLPA and qPCR assays, and could become a powerful technical support for large-scale screening of SMA.\n                  <\/jats:p>","DOI":"10.1186\/s40246-024-00676-8","type":"journal-article","created":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T17:01:37Z","timestamp":1727629297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluating the clinical efficacy of a long-read sequencing-based approach for carrier screening of spinal muscular atrophy"],"prefix":"10.1186","volume":"18","author":[{"given":"Ju","family":"Long","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanli","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,29]]},"reference":[{"issue":"1","key":"676_CR1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41572-022-00380-8","volume":"8","author":"E Mercuri","year":"2022","unstructured":"Mercuri E, Sumner CJ, Muntoni F, Darras BT, Finkel RS. Spinal muscular atrophy. Nat Reviews Disease Primers. 2022;8(1):52.","journal-title":"Nat Reviews Disease Primers"},{"issue":"21","key":"676_CR2","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.1007\/s00018-018-2849-1","volume":"75","author":"H Chaytow","year":"2018","unstructured":"Chaytow H, Huang YT, Gillingwater TH, Faller KME. The role of survival motor neuron protein (SMN) in protein homeostasis. Cell Mol Life Sci. 2018;75(21):3877\u201394.","journal-title":"Cell Mol Life Sci"},{"issue":"11","key":"676_CR3","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","volume":"96","author":"CL Lorson","year":"1999","unstructured":"Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA. 1999;96(11):6307\u201311.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"676_CR4","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1097\/GIM.0b013e318220d523","volume":"13","author":"TW Prior","year":"2011","unstructured":"Prior TW, Nagan N, Sugarman EA, Batish SD, Braastad C. Technical standards and guidelines for spinal muscular atrophy testing. Genet Medicine: Official J Am Coll Med Genet. 2011;13(7):686\u201394.","journal-title":"Genet Medicine: Official J Am Coll Med Genet"},{"issue":"1","key":"676_CR5","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s13023-017-0671-8","volume":"12","author":"IEC Verhaart","year":"2017","unstructured":"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.","journal-title":"Orphanet J Rare Dis"},{"issue":"5","key":"676_CR6","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/S1474-4422(12)70061-3","volume":"11","author":"E Mercuri","year":"2012","unstructured":"Mercuri E, Bertini E, Iannaccone ST. Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol. 2012;11(5):443\u201352.","journal-title":"Lancet Neurol"},{"issue":"6","key":"676_CR7","first-page":"661","volume":"41","author":"A Medical","year":"2024","unstructured":"Consensus Expert Group On Carrier Screening For Monogenic D, Genetic Counseling Group Of Medical Genetics Branch Of Chinese, Medical A, Hu T, Guo J, Liu S, Lu Y, et al. [Expert consensus over genetic counseling for carrier screening of spinal muscular atrophy]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi\u2009=\u2009Zhonghua Yixue Yichuanxue zazhi\u2009=\u2009Chinese. J Med Genet. 2024;41(6):661\u20138.","journal-title":"J Med Genet"},{"issue":"12","key":"676_CR8","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/s41582-020-00413-4","volume":"16","author":"E Mercuri","year":"2020","unstructured":"Mercuri E, Pera MC, Scoto M, Finkel R, Muntoni F. Spinal muscular atrophy - insights and challenges in the treatment era. Nat Reviews Neurol. 2020;16(12):706\u201315.","journal-title":"Nat Reviews Neurol"},{"issue":"7","key":"676_CR9","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/sj.ejhg.5201821","volume":"15","author":"M Smith","year":"2007","unstructured":"Smith M, Calabro V, Chong B, Gardiner N, Cowie S, du Sart D. Population screening and cascade testing for carriers of SMA. Eur J Hum Genetics: EJHG. 2007;15(7):759\u201366.","journal-title":"Eur J Hum Genetics: EJHG"},{"issue":"2","key":"676_CR10","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s004390000446","volume":"108","author":"MD Mailman","year":"2001","unstructured":"Mailman MD, Hemingway T, Darsey RL, Glasure CE, Huang Y, Chadwick RB, et al. Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMN1 copies on one chromosome. Hum Genet. 2001;108(2):109\u201315.","journal-title":"Hum Genet"},{"issue":"1","key":"676_CR11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/ejhg.2011.134","volume":"20","author":"EA Sugarman","year":"2012","unstructured":"Sugarman EA, Nagan N, Zhu H, Akmaev VR, Zhou Z, Rohlfs EM, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >\u200972,400 specimens. Eur J Hum Genetics: EJHG. 2012;20(1):27\u201332.","journal-title":"Eur J Hum Genetics: EJHG"},{"issue":"2","key":"676_CR12","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1086\/338627","volume":"70","author":"M Feldk\u00f6tter","year":"2002","unstructured":"Feldk\u00f6tter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. 2002;70(2):358\u201368.","journal-title":"Am J Hum Genet"},{"issue":"12","key":"676_CR13","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1016\/j.nmd.2006.08.011","volume":"16","author":"EL Arkblad","year":"2006","unstructured":"Arkblad EL, Darin N, Berg K, Kimber E, Brandberg G, Lindberg C, et al. Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy. 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Cell. 1995;80(1):155\u201365.","journal-title":"Cell"},{"issue":"9","key":"676_CR16","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.jmoldx.2022.05.001","volume":"24","author":"S Li","year":"2022","unstructured":"Li S, Han X, Xu Y, Chang C, Gao L, Li J, et al. Comprehensive analysis of spinal muscular atrophy: SMN1 Copy Number, Intragenic Mutation, and 2\u2009+\u20090 carrier analysis by third-generation sequencing. J Mol Diagnostics: JMD. 2022;24(9):1009\u201320.","journal-title":"J Mol Diagnostics: JMD"},{"key":"676_CR17","doi-asserted-by":"publisher","first-page":"117743","DOI":"10.1016\/j.cca.2023.117743","volume":"553","author":"J Bai","year":"2024","unstructured":"Bai J, Qu Y, Huang W, Meng W, Zhan J, Wang H, et al. A high-fidelity long-read sequencing-based approach enables accurate and effective genetic diagnosis of spinal muscular atrophy. Clin Chim Acta. 2024;553:117743.","journal-title":"Clin Chim Acta"},{"key":"676_CR18","doi-asserted-by":"publisher","first-page":"117496","DOI":"10.1016\/j.cca.2023.117496","volume":"548","author":"J Tan","year":"2023","unstructured":"Tan J, Zhang J, Sun R, Jiang Z, Wang Y, Ma D, et al. Evaluating the performance of four assays for carrier screening of spinal muscular atrophy. Clin Chim Acta. 2023;548:117496.","journal-title":"Clin Chim Acta"},{"issue":"2","key":"676_CR19","first-page":"160","volume":"43","author":"C Yanyan","year":"2021","unstructured":"Yanyan C, Miaomiao C, Fang S, Yujin Q, Jinli B, Hong W. Familial study of spinal muscular atrophy carriers with SMN1 (2\u2009+\u20090) genotype. Yi Chuan = Hereditas. 2021;43(2):160\u20138.","journal-title":"Yi Chuan = Hereditas"},{"issue":"14","key":"676_CR20","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1002\/elps.201000124","volume":"31","author":"CC Wang","year":"2010","unstructured":"Wang CC, Chang JG, Chen YL, Jong YJ, Wu SM. Multi-exon genotyping of SMN gene in spinal muscular atrophy by universal fluorescent PCR and capillary electrophoresis. Electrophoresis. 2010;31(14):2396\u2013404.","journal-title":"Electrophoresis"}],"container-title":["Human Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-024-00676-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40246-024-00676-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40246-024-00676-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,29]],"date-time":"2024-09-29T17:03:09Z","timestamp":1727629389000},"score":1,"resource":{"primary":{"URL":"https:\/\/humgenomics.biomedcentral.com\/articles\/10.1186\/s40246-024-00676-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,29]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["676"],"URL":"https:\/\/doi.org\/10.1186\/s40246-024-00676-8","relation":{},"ISSN":["1479-7364"],"issn-type":[{"value":"1479-7364","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,29]]},"assertion":[{"value":"10 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Ethics Committee of Qinzhou Maternal and Child Health Care Hospital. Informed consent was obtained from all participants or their legal guardians involved in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"110"}}