Identification of a PRX variant in a Chinese family with congenital cataract by exome sequencing

Background: Congenital cataract is a common cause of childhood vision impairment or blindness with genetic and clinical heterogeneity. The aim of this study was to identify the disease-associated gene in a Chinese family with congenital cataract. Methods: A four-generation Chinese family with three enrolled patients suffering from congenital cataract was studied. Detailed family history and clinical data of all the members were collected and recorded. Exome sequencing was applied in the proband to screen potential genetic variants, and then Sanger sequencing was used to verify the variant within the family. Results: A heterozygous variant, c.3673G> A (p.V1225M), in the periaxin gene (PRX) was identified in three patients and two asymptomatic individuals of the family. The variant was absent in the other three unaffected family members and in 3290 ethnically matched in-house controls from BGI-Shenzhen. Conclusions: By utilizing both exome sequencing and Sanger sequencing, we identified a missense variant in the PRX gene that is possibly associated with disease in this family. Our finding may broaden the spectrum of genes associated with congenital cataract, and may provide insights into lens development, pathogenic mechanism, future clinical genetic diagnosis and therapy of congenital cataract.