Next generation sequencing in children with isolated congenital cataract

Area of Science:

• Ophthalmology
• Genetics
• Pediatrics

Background:

• Congenital cataracts (CC) are a leading cause of preventable childhood blindness, with many cases remaining idiopathic.
• Genetic diagnosis of CC is essential for targeted management and avoiding unnecessary investigations.

Purpose of the Study:

• To investigate the genetic etiology of congenital cataracts (CC) in 10 families with previously unknown causes.
• To evaluate the utility of whole exome sequencing (WES) in diagnosing isolated CC.

Main Methods:

• Ten families with CC underwent comprehensive ophthalmological, metabolic, and genetic assessments.
• Whole exome sequencing (WES) was performed on probands, with variants confirmed by Sanger sequencing.

Main Results:

• Genetic variants were identified in 4 out of 10 families.
• A variant in *RAB3GAP1* (Martsolf syndrome), novel variants in *CRYGD* and *FYCO1*, and a known variant in *HSF4* were detected.
• Parental consanguinity was noted in 70% of the families, suggesting a higher prevalence of autosomal recessive CC.

Conclusions:

• Whole exome sequencing (WES) is an effective tool for diagnosing the genetic basis of congenital cataracts (CC).
• The high rate of consanguinity in the study population contributes to a higher incidence of autosomal recessive CC.
• Genetic diagnosis facilitates appropriate patient management and genetic counseling.