Identification of a Missense Mutation in GJA8 Gene in an Iranian Family with Autosomal Dominant Congenital Cataract

PURPOSE: To identify the causative mutations of autosomal dominant (AD) congenital cataracts in a large Iranian family. METHODS: The complete and accurate family history and clinical information of participants were collected. A total of 51 family members, including 22 affected and 29 unaffected individuals, were recruited in this study. We performed whole exome sequencing to reveal pathogenic mutation. We used amplification refractory mutation system polymerase chain reaction and Sanger sequencing techniques to confirm segregation in patients and also to rule it out in the healthy participants. RESULTS: A known missense mutation, c.827C>T (S276F), in GJA8 was identified. This mutation was confirmed in all patients. Neither all healthy family members nor 100 healthy individuals who served as controls from general population had this mutation. CONCLUSION: The missense mutation c. 827C>T in the GJA8 gene is associated with AD congenital lamellar cataract with complete penetrance in a six-generation Iranian family.