Genetic analysis and reproductive interventions in families affected by congenital cataracts: a study of 107 cases

Congenital cataract is a vision impairment that arises before birth or within the first year of life due to lens opacity, with genetic disorders being a significant contributing factor. The purpose of this study is to identify the pathogenic variants associated with congenital cataract to inform clinical diagnosis, treatment, reproductive intervention. Next-generation sequencing was performed on 107 families with congenital cataracts, followed by Sanger sequencing validation and familial analysis of candidate variants. RNA splicing pattern analysis was conducted on variants located near splicing sites. A total of 44 likely pathogenic or pathogenic variants (including 20 novel variants) in 46 families, and 19 variants of uncertain significance (VUS) in 19 families were identified, with a detection rate of 43.0%. A total of 14 VUS were sub-classified as "warm" or "hot" VUS based on Bayesian analysis. PGT or prenatal diagnosis was conducted in 26 families; follow-up revealed that 16 families opted for PGT and successfully delivered 10 healthy children. Among 10 families that pursued prenatal diagnosis after natural conception, 8 gave birth to healthy children.This study expanded the variant spectrum and providing valuable insights for the prevention and management of this condition.