Homozygosity Mapping of Pigmentary Retinopathy, Ataxia and Sudden Death to a Novel Locus on Chromsome 5q

Abstract

Abstract: : Purpose:To characterise the phenotype and identify the disease–causing gene in a family with pigmentary retinopathy, ataxia and sudden death. Methods: Ophthalmic and neurologic examinations and metabolic and mitochondrial screening were performed on 4 siblings (3 affected) from a small consanguineous family of Pakistani origin. A genome–wide search for homozygosity by descent was performed using DNA from 14 family members including the 3 deceased affected siblings, an unaffected sibling, the parents and more distant family members, using the GeneChip Human Mapping 10K Array from Affymetrix. Data were analysed using the software ALOHOMORA (Ruschendorf and Nürnberg, 2004). Results: Homozygosity by descent (HBD) was identified in all 3 affected children on chromosome 5q with a maximum lod score of 2.6. No other regions of HBD were identified. Conclusions: We have identified a novel chromosomal locus for a pigmentary retinopathy associated with ataxia and sudden death. The use of "SNP microarray" chips for genomewide scans is a powerful new tool for homozygosity mapping even in small families.

Keywords: linkage analysis • retinal degenerations: hereditary • gene mapping