First Major Gene Reported for Autosomal Recessive Retinitis Pigmentosa

Jacquelyn K Beals, PhD

October 06, 2008

October 6, 2008 — Mutations of EYS, a previously unreported gene on human chromosome 6, have been identified in families with autosomal recessive retinitis pigmentosa. The finding of 6 independent mutations of EYS in families of different ancestry "support[s] EYS as the first major gene reported for autosomal recessive retinitis pigmentosa," according to a study published online yesterday in Nature Genetics.

Autosomal recessive retinitis pigmentosa was previously linked to 26 genetic loci, but only 1 of these, a region on chromosome 6, was associated with more than 5% of cases. Shomi S. Bhattacharya, PhD, from the Department of Molecular Genetics, Institute of Ophthalmology, London, United Kingdom, and Institut de la Vision, Université Pierre et Marie Curie-Paris, France, and colleagues in Spain and England investigated this region to identify the responsible gene.

Of 110 genes in the region, 15 with known functions were excluded and 45 more were eliminated by screening. Genetic studies in 5 additional families with autosomal recessive retinitis pigmentosa enabled researchers to further narrow the region of candidate genes. A single region 100 kilobases long and containing 6 "independently predicted genes" had been deleted in affected members of 1 family studied and became the focus of screening.

Analysis eventually showed that the responsible gene includes 30 exons (regions of a gene incorporated in the final mRNA transcript, which is translated into a protein) associated previously with 9 other genes, as well as 13 exons previously unreported. Within these 43 exons, investigators have found "six independent mutations, including four deletions and two nonsense substitutions, all leading to premature stop codons in five unrelated families," according to the Nature Genetics article. These mutations were not found in any control individuals (n = 200).

EYS "is the largest gene identified to be expressed in the human eye and the fifth largest overall in the human genome," the article notes. The normal EYSgene product is thought to be a large protein consisting of 3145 amino acids and resembles a protein that influences optic architecture in the eye of Drosophila, houseflies, and certain other insects. The authors suggest that EYS may serve a related function, "maintaining the integrity of the photoreceptor cells in human retina."

Nat Genet. Published online October 5, 2008.

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