Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family.

Ophthalmic Genetics and Visual Function Branch, National Eye Institute,National Institutes of Health, Bethesda, MDPurpose: To investigate the genetic basis of autosomal recessive congenital cataracts in a consanguineous Pakistanifamily.Methods: All affected individuals underwent a detailed ophthalmological and clinical examination. Blood samples werecollected and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic microsatellitemarkers. Logarithm of odds (LOD) scores were calculated, and Eph-receptor type-A2 (EPHA2), residing in the criticalinterval, was sequenced bidirectionally.Results: The clinical and ophthalmological examinations suggested that all affected individuals have nuclear cataracts.Genome-wide linkage analyses localized the critical interval to a 20.78 cM (15.08 Mb) interval on chromosome 1p, witha maximum two-point LOD score of 5.21 at θ=0. Sequencing of EPHA2 residing in the critical interval identified a missensemutation: c.2353G>A, which results in an alanine to threonine substitution (p.A785T).Conclusions: Here, we report for the first time a missense mutation in EPHA2 associated with autosomal recessivecongenital cataracts.