{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:40:26Z","timestamp":1789580426993,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T00:00:00Z","timestamp":1411603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Institutes of Health\/National Institute of Child Health and Human Development","award":["HD057331"],"award-info":[{"award-number":["HD057331"]}]},{"name":"National Institutes of Health\/National Institute of Child Health and Human Development","award":["HD048895"],"award-info":[{"award-number":["HD048895"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Distal arthrogryposis (DA) syndromes are a group of disorders characterized by multiple congenital contractures. DA type 2A (DA2A or Freeman\u2013Sheldon syndrome), caused by mutations in <jats:italic>MYH3<\/jats:italic>, is typically considered the most severe of the DA syndromes. However, there is wide phenotypic variability among individuals with DA2A. We characterized genotype\u2010phenotype relationships in 46 families with DA2A. <jats:italic>MYH3<\/jats:italic> mutations were found in 43\/46 (93%) kindreds, with three mutations (p.T178I, p.R672C, and p.R672H) explaining 39\/43 (91%) of cases. Phenotypic severity varied significantly by genotype (<jats:italic>P<\/jats:italic>\u2009=\u20090.0055). Individuals with p.T178I were the most severely affected with both facial contractures and congenital scoliosis. Classification of individuals with DA2A into phenotypic groups of varying severity should facilitate providing families with more accurate information about natural history and suggests that individuals might benefit from personalized medical management motivated by <jats:italic>MYH3<\/jats:italic> genotype. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36762","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T19:04:36Z","timestamp":1411671876000},"page":"2808-2813","source":"Crossref","is-referenced-by-count":46,"title":["Genotype\u2010phenotype relationships in Freeman\u2013Sheldon syndrome"],"prefix":"10.1002","volume":"164","author":[{"given":"Anita E.","family":"Beck","sequence":"first","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle Washington"},{"name":"Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret J.","family":"McMillin","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle Washington"},{"name":"Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi I. 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