Genetic Variants In Patients With Bilateral Congenital Cataracts In A Large Cohort From North India

Congenital cataracts can result from systemic etiologies or genetic disorders. Literature studying the genotype-phenotype relations in pediatric cataracts from our population is scanty. Determining the precise genetic cause in a child will facilitate genetic counseling by identifying genetic conditions with the risk of recurrence in families, ensuring early screening and treatment for cataracts

Advanced Eye Centre, PGIMER, Chandigarh, India (Tertiary care referel Institute)

This was a prospective observational study, where we analyzed peripheral blood samples of pediatric patients with bilateral congenital cataracts via next-generation sequencing to identify cataract-causing genetic variants.

We enrolled 60 pediatric patients, with a mean age of 26.6 months, out of which there was a predominance of males (n=37; 61.6%). Variants were identified in 40 probands (66.6%). We identified pathogenic or likely pathogenic variants in 20 patients (33.3%) and 70% of these had no family history of cataract. Of the variants, we observed 18 single nucleotide variants (SNV) in 13 genes. SNVs in crystallin genes were most common, (4 out of 20) followed by SNVs in gap junction genes along with three novel variants. Two copy number variants (CNV) of varying size and genomic location were also reported. 

The variants in our cohort of pediatric cataract patients were very heterogeneous. Exome sequencing demonstrated a high diagnostic yield for a genetic variant in cases of bilateral congenital cataracts, even in the absence of family history.