Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
Mol Genet Genomic Med. 2022 Dec;10(12):e2042. doi: 10.1002/mgg3.2042. Epub 2022 Sep 7.
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.
远端型关节弯曲症（DA）是一组由关节和肌肉功能缺陷引起的常染色体显性遗传病，其特征是手足多个关节挛缩。根据临床特征，DA 可分为 10 种类型。DA 已被证实是由编码骨骼肌纤维收缩装置成分的基因突变引起的，如肌钙蛋白 I2（TNNI2）。
本研究报道了一个属于 DA2B 型的三代 DA 家族。受影响成员的临床特征具有遗传稳定性和一致性，手足严重畸形，两名受影响的成年人身材矮小。无面部异常。采集了 3 名受影响成员和 3 名健康成员的血液进行全外显子组测序和 Sanger 测序。
成功鉴定出 TNNI2 中的错义变异（NM_003282.4：c.525G>T：p.K175N），导致 TNNI2 第 175 位的赖氨酸被天冬酰胺取代。
TNNI2 中的变异 c.525G>T 解释了该家族的 DA 病因。该变异在中国人群中首次被发现，另一个研究也报道了相同的变异，但没有描述临床症状。我们的研究全面描述了 TNNI2 中的 c.525G>T 变异。
