Mutation Analysis of Families with Autosomal Dominant Congenital Cataract: A Recurrent Mutation in the CRYBA1/A3 Gene Causing Congenital Nuclear Cataract

ABSTRACT

Purpose: To identify the CRYBA1/A3 mutation spectrum and analyze the genotype-phenotype correlations in Chinese families with congenital cataract.

Methods: Family history and clinical data of 47 unrelated families with autosomal dominant congenital cataract (ADCC) were recorded. CRYBA1/A3 gene sequencing was applied to identify the causative mutation. Haplotypes were constructed using closely linked microsatellite markers and intragenic single-nucleotide polymorphisms (SNPs) to compare the affected haplotype in three families.

Results: Nuclear cataract was the most common type of ADCC in Chinese families, accounting for 42.6% (20/47). A recurrent CRYBA1/A3 deletion mutation (ΔG91) was identified in three families (6.4%) with nonprogressive nuclear congenital cataract. Different haplotypes segregated with the mutation in each family.

Conclusions: A recurrent ΔG91CRYBA1/A3 mutation occurs independently in 6.4% of the Chinese families with autosomal dominant nuclear cataracts and most likely represents a mutational hot spot, which underscores the relations between nonprogressive nuclear cataract and CRYBA1/A3.

KEYWORDS:

• Congenital cataract
• hot spot
• mutation
• CRYBA1/A3
• haplotype

Acknowledgments

We are grateful to the enthusiastic participation of all families in this study.

Funding

National Natural Science Foundation of China (51573101), Beijing Nova Program (Z151100000315096), Beijing Natural Science Foundation (7172056), and the priming scientific research foundation for the senior researchers in Beijing Tongren Hospital, Capital Medical University (2016-YJJ-GGL-010).

Disclosure statement

The authors declare no conflict of interest.