A mutation in GJA8 (p.P88Q) is associated with “balloon-like” cataract with Y-sutural opacities in a family of Indian origin

PURPOSE: To detect the underlying genetic defect in a family with three members in two generations affected with bilateral congenital cataract. METHODS: Detailed family history and clinical data were recorded. Mutation screening in the candidate genes, αA-crystallin (CRYAA), βA1-crystallin (CRYBA1), βB2-crystallin (CRYBB2), γA–γD-crystallins (CRYGA, CRYGB, CRYGC, and CRYGD), connexin-46 (GJA3), and connexin-50 (GJA8), was performed by bidirectional sequencing of the amplified products. RESULTS: Affected individuals had “balloon-like” cataract with prominent Y-sutural opacities. Sequencing of the candidate genes showed a heterozygous c.262C>A change in the gene for connexin 50 (GJA8), which is localized at 1q21, that resulted in the replacement of a highly conserved proline by glutamine (p.P88Q). This sequence change was not observed in 96 ethnically matched controls. CONCLUSIONS: We report a p.P88Q mutation in GJA8 associated with Y-sutural cataract in a family of Indian origin. Mutations of the same codon have previously been described in British families with pulverulent cataract, suggesting that modifying factors may determine the type of cataract.