{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:30:51Z","timestamp":1783405851938,"version":"3.54.6"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31501017"],"award-info":[{"award-number":["31501017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271946"],"award-info":[{"award-number":["81271946"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>SMAD6<\/jats:italic> variants have been reported in patients with radioulnar synostosis (RUS). This study aimed to investigate the genotypes and phenotypes for a large cohort of patients with RUS having mutant <jats:italic>SMAD6<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic DNA samples were isolated from 251 RUS sporadic patients (with their parents) and 27 RUS pedigrees. Sanger sequencing was performed for the <jats:italic>SMAD6<\/jats:italic> coding regions. For positive probands, co\u2010segregation and parental\u2010origin analysis of <jats:italic>SMAD6<\/jats:italic> variants and phenotypic re\u2010evaluation were performed for their family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 50 RUS probands with <jats:italic>SMAD6<\/jats:italic> variants (13 co\u2010segregated with RUS in pedigrees and 37 in RUS\u2010sporadic patients). Based on the new and previous data, we identified <jats:italic>SMAD6<\/jats:italic> mutated in 16\/38 RUS pedigrees and 61\/393 RUS sporadic patients, respectively. Overall, 93 <jats:italic>SMAD6<\/jats:italic> mutant patients with RUS were identified, among which 29 patients had unilateral RUS, where the left side was more involved than the right side (left:right\u00a0=\u00a020:9). Female protective effects and non\u2010full penetrance were observed, in which only 6.90% mothers (vs. ~50% fathers) of <jats:italic>SMAD6<\/jats:italic> mutant RUS probands had RUS. Pleiotropy was observed as a re\u2010evaluation of <jats:italic>SMAD6<\/jats:italic> mutant families identified: (a) three families had axial skeletal malformations; (b) two families had polydactyly; and (c) eight families had other known malformations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>SMAD6<\/jats:italic> was mutated in 42.11% RUS pedigrees and 15.52% RUS sporadic patients.<\/jats:p><jats:p>The RUS patients with <jats:italic>SMAD6<\/jats:italic> variants exhibit both non\u2010full\u2010penetrance, variable expressivity, pleiotropy, female protective effects, and the left side is more susceptible than the right side.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1850","type":"journal-article","created":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T06:39:23Z","timestamp":1640414363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A genotype and phenotype analysis of <i>SMAD6<\/i> mutant patients with radioulnar synostosis"],"prefix":"10.1002","volume":"10","author":[{"given":"Fang","family":"Shen","sequence":"first","affiliation":[{"name":"The Laboratory of Genetics and Metabolism Institute of Pediatric Medicine of Hunan Province Hunan Children\u2019s Hospital Hengyang Medical School, University of South China Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8673-1589","authenticated-orcid":false,"given":"Yongjia","family":"Yang","sequence":"additional","affiliation":[{"name":"The Laboratory of Genetics and Metabolism Institute of Pediatric Medicine of Hunan Province Hunan Children\u2019s Hospital Hengyang Medical School, University of South China Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Li","sequence":"additional","affiliation":[{"name":"The Laboratory of Genetics and Metabolism Institute of Pediatric Medicine of Hunan Province Hunan Children\u2019s Hospital Hengyang Medical School, University of South China Changsha China"},{"name":"Department of Hand Surgery Beijing Ji Shui Tan Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2511-961X","authenticated-orcid":false,"given":"Yu","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Laboratory of Genetics and Metabolism Institute of Pediatric Medicine of Hunan Province Hunan Children\u2019s Hospital Hengyang Medical School, University of South China Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenqing","family":"Luo","sequence":"additional","affiliation":[{"name":"The Laboratory of Genetics and Metabolism Institute of Pediatric Medicine of Hunan Province Hunan Children\u2019s Hospital Hengyang Medical School, University of South China Changsha 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