A new heterozygous mutation in the stop codon of CRYAB (p.X176Y) is liable for congenital posterior pole cataract in a Chinese family.

Abstract

Background: The present study aims to identify the underlying genetic defects in a Chinese family with autosomal dominant congenital cataracts (ADCC).Methods: Detailed family histories and clinical data were recorded. Targeted exome sequencing of 54 known cataract-associated genes combined with high-throughput next-generation sequencing was conducted followed by Sanger sequencing and bioinformatic analysis to identify the causative gene lesion for the family.Results: A four-generation Chinese family with posterior pole type cataract were enrolled. Enrichment of targeted genes revealed a new heterozygous p.X176Y mutation in the stop codon of αB-crystallin (CRYAB) gene, which resulted in the loss of the stop codon and prolongation of the mutant protein by 19 amino acid residues (p.X176Yfs19*). Sanger sequencing showed complete co-segregation with the disease. The elongated mutant protein was predicted to be pathogenic by forming new α-helix and random-coil in the secondary structure as well as producing an extended strand in the tertiary structure, potentially leading to increased hydrophobicity and reduced protein stability.Conclusions: Our report added a new mutation in the spectrum of congenital cataracts. The data suggested that X176 residue in the COOH-terminal is of crucial importance for the αB-crystallin protein function which was valuable for further study of the pathogenesis of congenital cataracts.Abbreviations:CRYAB: αB-crystallin; DNA: deoxyribonucleic acid; PCR: polymerase chain reaction; TES: targeted exome sequencing; ACD: αB-crystallin domain.

• Authors: Yinhui Yu, Jingjie Xu, Yue Qiao, Jinyu Li, Ke Yao
• Journal: Ophthalmic genetics (Ophthalmic Genet) Vol. 42 Issue 2 Pg. 139-143 (04 2021) ISSN: 1744-5094 [Electronic] England
• PMID: 33272090 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CRYAB protein, human
• Codon, Terminator
• alpha-Crystallin B Chain

Topics

• Adolescent
• Asian People (genetics)
• Cataract (congenital, genetics, pathology)
• Codon, Terminator
• Female
• Heterozygote
• Humans
• Male
• Mutation
• Pedigree
• alpha-Crystallin B Chain (genetics)