Spectrum of mutations that cause distal arthrogryposis types 1 and 2B

被引:57
作者
Beck, Anita E. [1 ,2 ]
McMillin, Margaret J. [1 ]
Gildersleeve, Heidi I. S. [1 ]
Kezele, Phillip R. [1 ]
Shively, Kathryn M. [1 ]
Carey, John C. [3 ]
Regnier, Michael [4 ]
Bamshad, Michael J. [1 ,2 ,5 ]
机构
[1] Univ Washington, Div Med Genet, Dept Pediat, Seattle, WA 98195 USA
[2] Seattle Childrens Hosp, Seattle, WA USA
[3] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT USA
[4] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA
[5] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA
基金
美国国家卫生研究院;
关键词
(all MeSH headings): arthrogryposis; distal arthrogryposis; distal arthrogryposis type 2B; distal arthrogryposis type 1; contracture; clubfoot; congenital vertical talus; congenital limb deformities; congenital foot deformities; congenital hand deformities; congenital upper extremity deformities; congenital lower extremity deformities; musculoskeletal abnormalities; human TNNI2 protein; human TNNT3 protein; human TPM2 protein; human MYH3 polypeptide; troponin I; troponin T; myosin heavy chains; muscle; skeletal muscle; SHELDON-HALL-SYNDROME; CLINICAL ANALYSIS; CHINESE FAMILY; VARIANT; MYOPATHY;
D O I
10.1002/ajmg.a.35809
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The distal arthrogryposis (DA) syndromes are a group of disorders characterized by non-progressive congenital contractures of the limbs. Mutations that cause distal arthrogryposis syndromes have been reported in six genes, each of which encodes a component of the contractile apparatus of skeletal myofibers. However, these reports have usually emanated from gene discovery efforts and thus potentially bias estimates of the frequency of pathogenic mutations at each locus. We characterized the spectrum of pathogenic variants in a cohort of 153 cases of DA1 (n=48) and DA2B (n=105). Disease-causing mutations in 56/153 (37%) kindreds including 14/48 (29%) with DA1 and 42/105 (40%) with DA2B were distributed nearly equally across TNNI2, TNNT3, TPM2, and MYH3. In TNNI2, TNNT3, and TPM2 the same mutation caused DA1 in some families and DA2B in others. We found no significant differences among the clinical characteristics of DA by locus or between each locus and DA1 or DA2B. Collectively, the substantial overlap between phenotypic characteristics and spectrum of mutations suggests that DA1 and DA2B should be considered phenotypic extremes of the same disorder. (c) 2013 Wiley Periodicals, Inc.
引用
收藏
页码:550 / 555
页数:6
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