title: Mutations in the RPGR gene cause X-linked cone dystrophy.
abstract: X-linked cone dystrophy is a type of hereditary retinal degeneration characterized by a progressive dysfunction of the day vision or photopic (cone) system with preservation of night vision or scotopic (rod) function. The disease presents with a triad of photophobia, loss of color vision and reduced central vision. This phenotype is distinct from retinitis pigmentosa (RP) in which there are prominent night and peripheral vision disturbances. X-linked cone dystrophy is a genetically heterogeneous disorder, with linkage to loci on Xp11.4--Xp21.1 (COD1, OMIM 304020) and Xq27 (COD2, OMIM 303800). COD1 maps to a region that harbors the RPGR gene, mutations in which account for >70% of patients with X-linked RP. The majority of these mutations reside in one purine-rich exon, ORF15, encoding 567 amino acids with a repetitive domain rich in glutamic acid residues. We mapped two families with X-linked cone dystrophy to the COD1 locus and identified two distinct mutations in ORF15 in the RPGR gene (ORF15+1343_1344delGG and ORF15+694_708del15) leading to a frame-shift and premature termination of translation in one case and a deletion of five amino acids in another. Consistent with expression of RPGR in rods and cones, our results show that mutations in RPGR, in addition to X-linked RP, can also cause cone-specific degeneration.
authors.affiliation: Cole Eye Institute, I-31, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Neal S
authors.initials: NS
authors.lastname: Peachey
authors.forename: Darius M
authors.initials: DM
authors.lastname: Moshfeghi
authors.forename: Sukanya
authors.initials: S
authors.lastname: Thirumalaichary
authors.forename: Lou
authors.initials: L
authors.lastname: Chorich
authors.forename: Yin Y
authors.initials: YY
authors.lastname: Shugart
authors.forename: Keke
authors.initials: K
authors.lastname: Fan
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003117:Color Vision Defects / Q000235:genetics; D005136:Eye Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames; D010375:Pedigree; D020795:Photophobia / Q000235:genetics; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D017384:Sequence Deletion; D014794:Visual Fields; D014960:X Chromosome
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; C099929:RPGR protein, human; D018698:Glutamic Acid