A TNNI2 variant c.525G>T causes distal arthrogryposis in a Chinese family.
A TNNI2 variant c.525G>T causes distal arthrogryposis in a Chinese family.
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DOI：
10.1002/mgg3.2042
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发表时间：
2022-12
影响因子：
2
通讯作者：
中科院分区：
文献类型：
--
作者：
远端关节弯曲症（DA）是一组继发于关节和肌肉功能缺陷的先天性常染色体显性遗传疾病，其特征为手足多发性关节挛缩。DA根据临床表现可分为10型。DA已被证实是由编码骨骼肌纤维的收缩装置组分的基因突变引起的，如肌钙蛋白I2（TNNI2）。在这项研究中，我们报告了一个属于DA2B型的三代DA家族。受影响的成员的临床特征是遗传稳定和一致的，手和脚严重畸形，两名受影响的成年人身材矮小。没有人表现出面部异常。采集三名受影响成员和三名健康成员的血液进行全外显子组测序和桑格测序。成功鉴定了TNNI2中的错义变体（NM_003282.4：c.525G>T：p.K175N），其导致TNNI2的175位氨基酸由赖氨酸取代为天冬酰胺。TNNI2中的变异c.525G>T解释了该家族中DA的原因。这是首次在中国人中发现这种变异，在另一项研究中也报告了相同的变异，但没有描述临床症状。我们的研究全面表征了TNNI2中的c.525G>T变体。一个三代患有远端关节弯曲症2B型的中国家族表现出身材矮小和手足严重畸形，但没有DA2B的典型面部异常表型。我们在该家族中鉴定了TNNI2 c.525G>T（p.K175N）的错义变体。
Distal arthrogryposis (DA) is a group of congenital autosomal‐dominant disorders secondary to defects in joint and muscle function, characterized by multiple joint contractures of the hands and feet. DA can be divided into 10 types according to clinical features. DA has been confirmed to be caused by mutations in genes encoding components of the contractile apparatus of skeletal muscle fibers, such as troponin I2 (TNNI2). In this study, we report a three‐generation DA family belonging to the DA2B type. The clinical characteristics of affected members are genetically stable and consistent, with severe deformities in hands and feet, and two affected adults had short stature. None exhibited facial abnormalities. Blood from three affected and three healthy members were collected for whole‐exome sequencing and Sanger sequencing. A missense variant in TNNI2 (NM_003282.4: c.525G>T: p.K175N) was successfully identified, which resulted in the substitution of amino acid at position 175 of TNNI2 from lysine to asparagines. The variant c.525G>T in TNNI2 explains the cause of DA in the family. This variant was identified in Chinese people for the first time, and the same variant had been reported in another study but no description of clinical symptoms. Our study comprehensively characterized the c.525G>T variant in TNNI2. A three‐generation Chinese family with Distal arthrogryposis type 2B show short stature and severe deformity of the hands and feet, but without the typical facial abnormality phenotype of DA2B. We identified a missense variant in TNNI2 c.525G>T(p.K175N) in this family.
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影响因子：
2
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.
通讯作者：
Bamshad, Michael J.
影响因子：
1.9
作者：
Shrimpton, AE;Hoo, JJ
通讯作者：
Hoo, JJ
影响因子：
4.8
作者：
Ramos, CHI
通讯作者：
Ramos, CHI
DOI：
10.1038/gim.2015.30
发表时间：
2015-05
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Richards S;Aziz N;Bale S;Bick D;Das S;Gastier-Foster J;Grody WW;Hegde M;Lyon E;Spector E;Voelkerding K;Rehm HL;ACMG Laboratory Quality Assurance Committee
通讯作者：
ACMG Laboratory Quality Assurance Committee
影响因子：
5.3
作者：
Jiang, Miao;Zhao, Xiuli;Li, Jianxin
通讯作者：
Li, Jianxin