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

[摘要] Purpose: To investigate the geneticbasis of autosomal recessive congenital cataracts in a consanguineousPakistani family. Methods: All affected individualsunderwent a detailed ophthalmological and clinical examination. Bloodsamples were collected and genomic DNAs were extracted. A genome-widescan was performed with polymorphic microsatellite markers. Logarithmof odds (LOD) scores were calculated, and Eph-receptor type-A2 (EPHA2),residinginthecriticalinterval, was sequenced bidirectionally. Results: The clinical andophthalmological examinations suggested that all affected individualshave nuclear cataracts. Genome-wide linkage analyses localized thecritical interval to a 20.78 cM (15.08 Mb) interval on chromosome 1p,with a maximum two-point LOD score of 5.21 at θ=0. Sequencing of EPHA2residing in the critical interval identified a missense mutation:c.2353G>A, which results in an alanine to threonine substitution(p.A785T). Conclusions: Here, we report for thefirst time a missense mutation in EPHA2 associated withautosomal recessive congenital cataracts.

[学科分类] 生物化学/生物物理