A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract.

C ataract results from a loss in transparency of the crystalline lens. Worldwide, there are an estimated 20 million people blind (Snellen visual acuity of 3/60 or less) as a result of cataract. Despite effective surgical treatment, demand outstrips supply in both Western and developing countries, for many reasons, 3 and other disease modifying strategies must be considered. A strong genetic predisposition to the development of congenital cataract and age related cataract has been well documented. 5 Inherited cataract accounts for at least 50% of all congenital cataracts, and shows marked interand intrafamilial variation. Twin studies on age related cataracts in the United Kingdom estimate that two thirds of cortical cataract and at least half of nuclear cataracts can be explained by genetic factors. 9 Previous genetic studies of congenital cataracts identified connexin 50 (Cx50) as a cataract related gene. Here we report a novel heterozygous R23T mutation in the GJA8 gene (MIM#600897) encoding connexin 50, in an Iranian family affected by a progressive autosomal dominant congenital nuclear cataract. In addition, to determine the genetic contribution of connexin 50 mutations to the basis of congenital and age related cataracts for our mutation (R23T) and the other three published Cx50 mutations (P88S, E48K, and I247M), two additional patient populations were screened for those changes.