Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans.
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 a 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 RP. Expression studies support the predominant expression of this gene in the retina, with equal expression in the retinal pigment epithelium, photoreceptor, 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 humans.
Zangerl
Barbara
B
Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Goldstein
Orly
O
Philp
Alisdair R
AR
Lindauer
Sarah J P
SJ
Pearce-Kelling
Susan E
SE
Mullins
Robert F
RF
Graphodatsky
Alexander S
AS
Ripoll
Daniel
D
Felix
Jeanette S
JS
Stone
Edwin M
EM
Acland
Gregory M
GM
Aguirre
Gustavo D
GD
D000595:Amino Acid Sequence; D000818:Animals; D001947:Breeding; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D020224:Expressed Sequence Tags; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D015723:Gene Library; D005808:Genes, Recessive; D023281:Genomics; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D012162:Retinal Degeneration / Q000235:genetics / Q000662:veterinary*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D018076:DNA, Complementary; D005136:Eye Proteins; C583558:PRCD protein, human