Missense mutations in the alpha-B crystallin gene (CRYAB) have been reported in desmin-related myopathies with or without cardiomyopathy and have also been reported in families with only a cataract phenotype. Dilated cardiomyopathy (DCM) is a disorder with a highly heterogeneous genetic etiology involving more than 60 causative genes, hindering genetic diagnosis. In this study, we performed whole genome sequencing on 159 unrelated patients with DCM and identified an unusual stop-loss pathogenic variant in NM_001289808.2:c.527A>G of CRYAB in one patient. The mutant alpha-B crystallin protein is predicted to have an extended strand with addition of 19 amino acid residues, p.(Ter176TrpextTer19), which may contribute to aggregation and increased hydrophobicity of alpha-B crystallin. The proband, diagnosed with DCM at age 32, had a history of bilateral congenital cataracts but had no evidence of myopathy or associated symptoms. He also has a 10-year-old child diagnosed with bilateral congenital cataracts with the same CRYAB variant. This study expands the mutational spectrum of CRYAB and deepens our understanding of the complex phenotypes of alpha-B crystallinopathies.

据报道，伴有或不伴有心肌病的结蛋白相关肌病中存在α-B 晶状体蛋白基因 ( CRYAB ) 的错义突变，并且在仅有白内障表型的家族中也有报道。扩张型心肌病 (DCM) 是一种具有高度异质性遗传病因的疾病，涉及 60 多个致病基因，阻碍了基因诊断。在本研究中，我们对 159 名无关的 DCM 患者进行了全基因组测序，并在一名患者的CRYAB NM_001289808.2:c.527A>G 中发现了一个不寻常的终止致病性变异。突变体 α-B 晶状体蛋白预计具有一条延伸链，其中添加了 19 个氨基酸残基 p.(Ter176TrpextTer19)，这可能有助于 α-B 晶状体蛋白的聚集和疏水性增加。先证者在 32 岁时被诊断患有 DCM，有双侧先天性白内障病史，但没有肌病或相关症状的证据。他还有一个 10 岁的孩子，被诊断患有双侧先天性白内障，具有相同的CRYAB变异。这项研究扩大了CRYAB的突变谱，加深了我们对 α-B 晶体病复杂表型的理解。