A novel CRYAB gene variation and clinical features in a family with congenital cataracts
10.3760/cma.j.cn115989-20250319-00086
- VernacularTitle:先天性白内障一家系 CRYAB基因新变异及临床特点分析
- Author:
Rong ZHANG
1
;
Yacong WANG
;
Kai LI
;
Jie BAI
;
Yuqiao MA
;
Tingting ZHANG
;
Hong ZHANG
;
Sudan LIU
Author Information
1. 石家庄市第四医院眼科，石家庄 050000
- Publication Type:Journal Article
- Keywords:
Congenital cataract;
Heredity;
Gene variation;
CRYAB gene;
Clinical feature
- From:
Chinese Journal of Experimental Ophthalmology
2025;43(12):1120-1125
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical features and pathogenic genes of a family with congenital cataracts.Methods:A pedigree analysis was performed.A Han Chinese family initially diagnosed with congenital cataracts at The Fourth Hospital of Shijiazhuang in March 2024 was enrolled.The proband and selected family members underwent detailed ophthalmic examinations.Potential cataract-associated genetic variants in the proband were identified using whole exome sequencing (WES). Sanger sequencing was employed to confirm the presence of these variants in the proband and other family members.The identified variants were analyzed in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). This study adhered to the Declaration of Helsinki.The research protocol was approved by the Ethics Committee of The Fourth Hospital of Shijiazhuang (No.20230074). Both the subjects and their guardians were informed of the study purpose and voluntarily signed the informed consent form.Results:The pedigree included four generations comprising 15 individuals, with three patients identified across the second, third, and fourth generations.These cases included two males and one female, specifically the proband, his mother, and his eldest son.The observed inheritance pattern aligned with an autosomal dominant mode, characterized by the clinical presentation of bilateral cataracts.WES identified a novel frameshift insertion variant c. 270_271insA in exon 2 of the CRYAB gene in the proband, resulting in a valine-to-serine substitution at amino acid position 91.This variant induced early termination of translation following the expression of two additional amino acids, loss of 84 amino acids (p.V91Sfs2) and the production of a functionally impaired protein.The Sanger sequencing validation results were consistent with the co-segregation.According to the ACMG classification criteria (PM2+ PP1+ PVS1), the variant was classified as likely pathogenic. Conclusions:The frameshift insertion variant c. 270_271insA (p.V91Sfs2) in exon 2 of the CRYAB gene is likely the pathogenic cause of congenital cataract in this family.This is the first report of this variant.
