Identical Mutation in a Novel Retinal Gene Causes Progressive Rod-Cone Degeneration (prcd) in Dogs and Retinitis Pigmentosa in Man

• Published in: Genomics (San Diego, Calif.) Calif.), 2006-08, Vol.88 (5), p.551-563
• Main Authors: Zangerl, Barbara, Goldstein, Orly, Philp, Alisdair R., Lindauer, Sarah J.P., Pearce-Kelling, Susan E., Mullins, Robert F., Graphodatsky, Alexander S., Ripoll, Daniel, Felix, Jeanette S., Stone, Edwin M., Acland, Gregory M., Aguirre, Gustavo D.
• Format: Article
• Language: English
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2006.07.007

Progressive rod-cone degeneration ( prcd ) is a late-onset, autosomal recessive photoreceptor degeneration of dogs, and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease relevant interval was reduced to a 106 Kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds, and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease relevant interval. The complete cDNA of one of these, PRCD , was cloned in dog, human and mouse. The gene codes for a 54 amino acid (aa) protein in dog and human, and 53 aa protein in the mouse; the first 24 aa, coded for by exon 1, are highly conserved in 14 vertebrate species. A homozygous mutation (TGC → TAC) in the second codon shows complete concordance with the disorder in 18 different dog breeds/breed varieties tested. The same homozygous mutation was identified in a human patient from Bangladesh with autosomal recessive (ar) RP. Expression studies support the predominant expression of this gene in the retina, with equal expression in the retinal pigment epithelium (RPE), photoreceptors and ganglion cell layers. This study provides strong evidence that a mutation in the novel gene, PRCD , is the cause of autosomal recessive retinal degeneration in both dogs and man.