A novel mutation in the OAR domain of PITX3 associated with congenital posterior subcapsular cataract

Abstract

Background: Congenital cataract is the most common cause of blindness among children worldwide. The aim of this study was to identify causative mutations in a Chinese family with isolated autosomal dominant posterior subcapsular cataract. Methods: The proband and her parents underwent full ophthalmological examinations. DNA was extracted from the participants' peripheral venous blood. The mutation was identified via panel-based next-generation sequencing (NGS) and was validated via Sanger sequencing. Results: Posterior subcapsular lenticular opacity was observed in both of the proband's eyes. The novel deletion mutation c.797-814del, p.Ser266-Ala271del in the PITX3 gene was identified in the proband and her father. This mutation is located within the otp/aristaless/rax (OAR) domain at the COOH-terminus of the protein, which functions in DNA binding and transactivation. This mutation would result in a deletion of 6 amino acid residues at the C terminal of the protein. Conclusions: The mutation c.797-814del, p.Ser266-Ala271del is a novel mutation in the conserved DNA-binding OAR domain of PITX3 that causes congenital cataract.