{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:19:58Z","timestamp":1787239198939,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Population-wide carrier screening for spinal muscular atrophy (SMA) is recommended by professional organizations to facilitate informed reproductive options. However, genetic screening for SMN1 2 + 0 carriers, accounting for 3%\u20138% of all SMA carriers, has been challenging due to the large gene size and long distance between the 2 SMN genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we repurposed a previously developed long-read sequencing-based approach, termed comprehensive analysis of SMA (CASMA), to identify SMN1 2 + 0 carriers through haplotype analysis in family trios (CASMA-trio). Bioinformatics pipelines were developed for accurate haplotype analysis and SMN1 2 + 0 deduction. Seventy-nine subjects from 24 families composed of, at the minimum, 3 were enrolled, and CASMA-trio was employed to determine whether an index subject with 2 SMN1 copies was a 2 + 0 carrier in these families. For the proof-of-principle, SMN2 2 + 0 was also analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 16 subjects with 2 SMN1 copies, CASMA-trio identified 5 subjects from 4 families as SMN1 2 + 0 carriers, which was consistent with pedigree analysis involving an affected proband. CASMA-trio also identified SMN2 2 + 0 in six out of 43 subjects with 2 SMN2 copies. Additionally, CASMA-trio successfully determined the distribution pattern of SMN1 and SMN2 genes on 2 alleles in all 79 subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CASMA-trio represents an effective and universal approach for SMN1 2 + 0 carriers screening, as it does not reply on the presence of an affected proband, certain single-nucleotide polymorphisms, ethnicity-specific haplotypes, or complicated single-nucleotide polymorphism analysis across 3 generations. Incorporating CASMA-trio into existing SMA carrier screening programs will greatly reduce residual risk ratio.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvad152","type":"journal-article","created":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T11:06:41Z","timestamp":1694862401000},"page":"1295-1306","source":"Crossref","is-referenced-by-count":8,"title":["An Effective and Universal Long-Read Sequencing-Based Approach for\n                    <i>SMN1<\/i>\n                    2 + 0 Carrier Screening through Family Trio Analysis"],"prefix":"10.1093","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1105-5571","authenticated-orcid":false,"given":"Shuyuan","family":"Li","sequence":"first","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxin","family":"Chang","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahan","family":"Zhan","sequence":"additional","affiliation":[{"name":"Berry Genomics Corporation , Beijing 102200 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-737X","authenticated-orcid":false,"given":"Renyi","family":"Hua","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Mao","sequence":"additional","affiliation":[{"name":"Berry Genomics Corporation , Beijing 102200 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Wang","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai 200030 , China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"2023110702324415800_hvad152-B1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1097\/GIM.0b013e318220d523","article-title":"Technical standards and guidelines for spinal muscular atrophy testing","volume":"13","author":"Prior","year":"2011","journal-title":"Genet Med"},{"key":"2023110702324415800_hvad152-B2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining 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probe amplification improves diagnostics in spinal muscular atrophy","volume":"16","author":"Arkblad","year":"2006","journal-title":"Neuromuscul Disord"},{"key":"2023110702324415800_hvad152-B12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10048-006-0051-3","article-title":"Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification","volume":"7","author":"Scarciolla","year":"2006","journal-title":"Neurogenetics"},{"key":"2023110702324415800_hvad152-B13","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1039\/c1lc20126c","article-title":"Multiplex digital PCR: breaking the one target per color barrier of quantitative PCR","volume":"11","author":"Zhong","year":"2011","journal-title":"Lab Chip"},{"key":"2023110702324415800_hvad152-B14","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1007\/s10072-020-04365-x","article-title":"SMN1 Gene copy number analysis for spinal muscular atrophy (SMA) in a Turkish cohort by CODE-SEQ technology, an integrated solution for detection of SMN1 and SMN2 copy numbers and the \u201c2 + 0\u201d genotype","volume":"41","author":"Ceylan","year":"2020","journal-title":"Neurol Sci"},{"key":"2023110702324415800_hvad152-B15","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1590\/S1415-47572012000600010","article-title":"Molecular analysis of spinal muscular atrophy: a genotyping protocol based on TaqMan((R)) real-time PCR","volume":"35","author":"Godinho FM","year":"2012","journal-title":"Genet Mol Biol"},{"key":"2023110702324415800_hvad152-B16","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/gim.2016.215","article-title":"The next generation of population-based spinal muscular atrophy carrier screening: comprehensive pan-ethnic SMN1 copy-number and sequence variant analysis by massively parallel sequencing","volume":"19","author":"Feng","year":"2017","journal-title":"Genet 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atrophy, genotype-phenotype correlation, and implications for genetic counseling","volume":"64","author":"Wirth","year":"1999","journal-title":"Am J Hum Genet"},{"key":"2023110702324415800_hvad152-B20","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/jhg.2015.16","article-title":"A new method for SMN1 and hybrid SMN gene analysis in spinal muscular atrophy using long-range PCR followed by sequencing","volume":"60","author":"Kubo","year":"2015","journal-title":"J Hum Genet"},{"key":"2023110702324415800_hvad152-B21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/humu.20092","article-title":"Molecular analysis of SMA patients without homozygous SMN1 deletions using a new strategy for identification of SMN1 subtle mutations","volume":"24","author":"Clermont","year":"2004","journal-title":"Hum Mutat"},{"key":"2023110702324415800_hvad152-B22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.nmd.2019.11.010","article-title":"Identification of novel SMN1 subtle mutations using an allelic-specific RT-PCR","volume":"30","author":"Xu","year":"2020","journal-title":"Neuromuscul Disord"},{"key":"2023110702324415800_hvad152-B23","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.jmoldx.2022.05.001","article-title":"Comprehensive analysis of spinal muscular atrophy: SMN1 copy number, intragenic mutation, and 2 + 0 carrier analysis by third-generation sequencing","volume":"24","author":"Li","year":"2022","journal-title":"J Mol Diagn"},{"key":"2023110702324415800_hvad152-B24","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/cge.12222","article-title":"Improving detection and genetic counseling in carriers of spinal muscular atrophy with two copies of the SMN1 gene","volume":"85","author":"Alias","year":"2014","journal-title":"Clin Genet"},{"key":"2023110702324415800_hvad152-B25","first-page":"160","article-title":"Familial study of spinal muscular atrophy carriers with SMN1 (2 + 0) 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