Linkage Analysis of Pakistani Families with Night Blindness

Abstract

Sense of vision is associated with the eye which has incredibly complex structure. Retina is the most important part of eye, which is mainly associated with processes like phototransduction and regeneration of visual pigments. Retinal diseases involving hereditary ones and also blindness represent the dysfunction or degeneration of the retina exhibiting profound visual impairments. Congenital stationary night blindness (CSNB) is also a hereditary dysfunction of retina in which the pathway of visual cascade associated with the rod cells become defective resulting in the loss of night vision. Patterns of inheritance followed by CSNB which is a rare and non progressive retinal condition are autosomal dominant, autosomal recessive or X-linked. The seven candidate genes (SAG, CCDC66, GRM6, CABP4, RDH5, TRPM1 and SLC24A1) reported yet for CSNB are involved in visual cascade. In the current study two Pakistani families (A and B) from the lower areas of Sindh province were investigated. These families were multigenerational, had consanguineous marriages and affected individuals presented symptoms of autosomal recessive CSNB. Linkage analysis by homozygosity mapping was employed for identification of candidate genes in both families by genotyping the available family members with microsatellite markers flanking already known genes for CSNB. The data from the genotyping of loci was further analyzed by using easyLINKAGE plus version 5.02 and a non signficant value of LOD score was obtained for both families confirming the exclusion of linkage to already known genes, thus suggesting the involvement of novel gene/loci in both families. The study proposes further research for better understanding and exploring of novel genes responsible for CSNB in family A and B by the help of whole genome scan through microsatellite markers or SNP markers.