Identification of 3 Novel Mutations in LCA5 (Lebercilin) in Leber’s Congenital Amaurosis Families

Abstract

Purpose: : Leber’s congenital amaurosis (LCA) is an inherited, early onset, severe form of retinal degeneration. Studies into the molecular genetics of LCA have identified fourteen different LCA genes and these account for 70% of LCA cases. The purpose of this study was to identify the mutated gene in a cohort of LCA families from Pakistan.

Methods: : Pooled DNA samples from affected individuals from each family were processed using Affymetrix 5.0 SNP microarrays. Regions of homozygosity were identified using IBDfinder software and confirmed by genotyping fluorescently labelled microsatellites in all available family members. The coding exons of LCA5 were amplified by PCR and sequenced using standard protocols.

Results: : Three novel LCA5 mutations were identified. In exon 2 we identified two nonsense mutations, c.238 C>T (R80X) and c.629delCT (S210X). In exon 7 we identified a frameshift mutation, c.1550delGA (R517fsX519).

Conclusions: : To date, eight mutations in LCA5 have been published. Here we present three novel mutations in three unrelated LCA families. Our results suggest that LCA5 mutations are a common cause of LCA in Pakistan.

Keywords: genetics • retinal degenerations: hereditary • visual impairment: neuro-ophthalmological disease