Next generation sequencing in children with isolated congenital cataract

Abstract

Purpose

Congenital cataracts (CC) are a preventable cause of childhood blindness, accounting for approximately 10% of cases. A significant portion of CC cases remains idiopathic. Genetic diagnosis can eliminate unnecessary tests and ensure appropriate follow-up and treatment. This study aimed to evaluate the etiology of CC without known etiological reasons in 10 families using whole exome sequencing (WES).

Methods

Ten families participated in this study, with all patients undergoing comprehensive ophthalmological, metabolic, and genetic assessments. DNA samples from the probands were analyzed using WES, and variants were verified and validated through Sanger sequencing.

Results

Of the 10 patients diagnosed with isolated CC, 9 (90%) had bilateral cataracts, and 1 (10%) had unilateral cataract. Nuclear type cataracts were detected in 8 (80%) patients, while polar type cataracts were found in 2 (20%) patients. Parental consanguinity was present in 7 out of the 10 families. An unidentified variant in the RAB3GAP1 gene (c.491C > G) associated with Martsolf syndrome was found in one patient. Two novel and one previously identified gene variants associated with CC were detected in 3 of the remaining 9 patients: a novel c.463C > T in CRYGD, a previously identified c.965dup in HSF4, and a novel c.3330C > A in FYCO1.

Conclusion

The high rate of consanguineous marriages in Turkey (23.3%) increases the incidence of autosomal recessive (AR) diseases, explaining the higher prevalence of AR CC despite its usual autosomal dominant inheritance. In conclusion, WES is a valuable tool in determining the etiology of isolated CC.