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CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy

Journal of Human Genetics volume 69, pages 159–162 (2024)Cite this article

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Abstract

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.

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Acknowledgements

This work was performed as part of the National Project of Bio Big Data. We thank the patient and his family for participating to this study.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea

    Changhee Ha, Young-gon Kim, Ja-Hyun Jang, Jong-Won Kim & Mi-Ae Jang

  2. Division of Cardiology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea

    Darae Kim, Minjung Bak & Jin-Oh Choi

  3. Clinical Genome Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea

    Jong-Ho Park & Jong-Won Kim

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  1. Changhee Ha
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Correspondence to Jin-Oh Choi or Mi-Ae Jang.

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This study was approved by the Institutional Review Board of Samsung Medical Center (IRB No.: SMC 2020-10-042).

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Ha, C., Kim, D., Bak, M. et al. CRYAB stop-loss variant causes rare syndromic dilated cardiomyopathy with congenital cataract: expanding the phenotypic and mutational spectrum of alpha-B crystallinopathy. J Hum Genet 69, 159–162 (2024). https://doi.org/10.1038/s10038-023-01218-1

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