Clinical and Genetic Study of X–Linked Cone Dystrophy

Abstract

Purpose: : The cone dystrophies are characterized by progressive dysfunction of the photopic (cone–mediated) system, presenting with photophobia, loss of color vision and reduced central visual acuity. Cone dystrophy is genetically heterogeneous and may present as an autosomal dominant, autosomal recessive, or X–linked recessive trait. Three loci for X–linked cone dystrophy have been mapped, and one gene, RPGR has been identified. We investigated a large Utah pedigree spanning six generations with 177 individuals with X–linked cone dystrophy.

Methods: : Peripheral blood was taken from 23 members, including 10 affected males and 5 carriers. Participants underwent ophthalmologic examination, fundus photography and an electroretinogram. Genotyping to X–linked cone dystrophy loci (COD1, COD2, and COD3) were performed, and mutation screening of RPGR was performed by PCR and direct DNA sequencing.

Results: : Age of onset ranges from 1–3 years, visual acuity ranges from 20/70 in children to 20/400 in older adults. Direct sequencing showed no RPGR mutation. Linkage analysis mapped the disease gene to COD2 locus with maximal lod score of 2.781175 with GATA83F09.

Conclusions: : We mapped a large Utah family with cone dystrophy to COD2. Fine mapping and positional cloning are in progress. Identification of the disease gene for COD2 will increase our understanding of cone dystrophy and provide new therapeutic avenues.

Keywords: degenerations/dystrophies • color vision • gene mapping