Spectrum of mutations that cause distal arthrogryposis types 1 and 2B.
Spectrum of mutations that cause distal arthrogryposis types 1 and 2B.
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DOI：
10.1002/ajmg.a.35809
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发表时间：
2013-03
影响因子：
2
通讯作者：
Bamshad, Michael J.
中科院分区：
文献类型：
--
作者：
Beck, Anita E.;McMillin, Margaret J.;Gildersleeve, Heidi I. S.;Kezele, Phillip R.;Shively, Kathryn M.;Carey, John C.;Regnier, Michael;Bamshad, Michael J.
关键词：
(all MeSH headings): arthrogryposisdistal arthrogryposisdistal arthrogryposis type 2Bdistal arthrogryposis type 1contractureclubfootcongenital vertical taluscongenital limb deformitiescongenital foot deformitiescongenital hand deformitiescongenital upper extremity deformitiescongenital lower extremity deformitiesmusculoskeletal abnormalitieshuman TNNI2 proteinhuman TNNT3 proteinhuman TPM2 proteinhuman MYH3 polypeptidetroponin Itroponin Tmyosin heavy chainsmuscleskeletal muscle
远端关节弯曲综合征是一组以非进行性先天性肢体挛缩为特征的疾病。导致远端关节弯曲综合征的突变已被报道在六个基因中，每个基因编码骨骼肌纤维收缩装置的一个组成部分。然而，这些报告通常源于基因发现的努力，因此可能会对每个位点的致病性突变频率进行偏倚估计。我们对153例DA 1（n = 48）和DA 2B（n = 105）病例的致病性变异谱进行了表征。56/153（37%）家族中的致病突变（包括14/48（29%）DA 1和42/105（40%）DA 2B）在TNNI 2、TNT 3、TPM 2和MYH 3中几乎均匀分布。在TNNI 2、TNT 3和TPM 2中，相同的突变在一些家族中引起DA 1，在另一些家族中引起DA 2B。我们发现，DA的临床特征之间没有显着差异的基因座或每个基因座和DA 1或DA 2B之间。总的来说，表型特征和突变谱之间的大量重叠表明DA 1和DA 2B应被视为同一疾病的表型极端。
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 suggest that DA1 and DA2B should be considered phenotypic extremes of the same disorder.
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