{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:46Z","timestamp":1753861786340,"version":"3.41.2"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["21JCZDJC01030"],"award-info":[{"award-number":["21JCZDJC01030"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Autosomal recessive spinal muscular atrophy (SMA) is a leading cause of infant and child mortality, with homozygous deletion in exon 7 of the <jats:italic>SMN1<\/jats:italic> gene being a major genetic cause. However, routine genetic testing methods may overlook structural variants outside of exon 7, potentially leading to misdiagnosis of SMA patients. Here, we reported two Chinese SMA patients who primarily exhibited developmental delays. Physical examinations revealed markedly reduced muscle strength and tone in their extremities, and electromyography suggested extensive neurogenic damage in the anterior horn of the spinal cord. The MLPA results indicated a single copy number of <jats:italic>SMN1<\/jats:italic> in both patients, which is inconsistent with the typical genetic pattern of SMA. Through RNA sequencing and ultra\u2010long read sequencing, we ultimately identified a rare structural variant involving the deletion of exons 2a\u20135 in both unrelated patients. This confirmed the presence of compound heterozygous variants in the <jats:italic>SMN1<\/jats:italic> gene as the actual genetic cause. To our knowledge, this is the first case where a combination of RNA sequencing and ultra\u2010long read sequencing has been used to diagnose SMA. We demonstrated the significant value of RNA sequencing in cases where children are highly suspected of having SMA but present negative results in routine genetic testing. This underscores the crucial role of accurate genetic testing methods in achieving early diagnosis of SMA.<\/jats:p>","DOI":"10.1002\/ajmg.a.63917","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T07:13:46Z","timestamp":1730790826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delayed Diagnosis of Spinal Muscular Atrophy in Two Chinese Families due to Novel <i>SMN1<\/i> Deletions"],"prefix":"10.1002","volume":"197","author":[{"given":"Yan","family":"Dong","sequence":"first","affiliation":[{"name":"Graduate College Tianjin Medical University  Tianjin China"},{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Graduate College Tianjin Medical University  Tianjin China"},{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"},{"name":"Department of Neurology Tianjin Children's Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Multi\u2010Omics Precision Diagnosis Technology for Neurological Diseases in Tianjin Tianjin Kingmed Center for Clinical Laboratory  Tianjin China"},{"name":"Tianjin Kingmed Center for Clinical Laboratory  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changshun","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Multi\u2010Omics Precision Diagnosis Technology for Neurological Diseases in Tianjin Tianjin Kingmed Center for Clinical Laboratory  Tianjin China"},{"name":"Tianjin Kingmed Center for Clinical Laboratory  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiran","family":"Li","sequence":"additional","affiliation":[{"name":"Graduate College Tianjin Medical University  Tianjin China"},{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ximeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Graduate College Tianjin Medical University  Tianjin China"},{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Yu","sequence":"additional","affiliation":[{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"},{"name":"Department of Neurology Tianjin Children's Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"},{"name":"Department of Neurology Tianjin Children's Hospital  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianbo","family":"Shu","sequence":"additional","affiliation":[{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"},{"name":"Tianjin Pediatric Research Institute Tianjin Children's Hospital  Tianjin China"},{"name":"Tianjin Key Laboratory of Birth Defects for Prevention and Treatment  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7265-9387","authenticated-orcid":false,"given":"Chunquan","family":"Cai","sequence":"additional","affiliation":[{"name":"Tianjin Children's Hospital Children's Hospital of Tianjin University  Tianjin China"},{"name":"Tianjin Pediatric Research Institute Tianjin Children's Hospital  Tianjin China"},{"name":"Tianjin Key Laboratory of Birth Defects for Prevention and Treatment  Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.01.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2102047"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/338627"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702752"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-1025-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1238"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706198"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70061-3"},{"issue":"15","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241511939","article-title":"Spinal Muscular Atrophy: The Past, Present, and Future of Diagnosis and Treatment","volume":"24","author":"Nishio H.","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2008.08.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02252"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1704117114"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32833f3046"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-102319-103602"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63917","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:16:34Z","timestamp":1748348194000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,4]]},"references-count":16,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/ajmg.a.63917"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63917","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2024,11,4]]},"assertion":[{"value":"2024-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63917"}}