Mutations in the RPGR gene cause X-linked cone dystrophy

• Published in: Human molecular genetics 2002-03, Vol.11 (5), p.605-611
• Main Authors: ZHENGLIN YANG, PEACHEY, Neal S, MOSHFEGHI, Darius M, THIRUMALAICHARY, Sukanya, CHORICH, Lou, SHUGART, Yin Y, KEKE FAN, KANG ZHANG
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Classical genetics, quantitative genetics, hybrids; COD2 gene; Color Vision Defects - genetics; Eye Proteins; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Glutamic Acid - metabolism; Heterozygote; Human; Humans; Male; Medical sciences; Mutation - genetics; Open Reading Frames; Ophthalmology; Pedigree; Photophobia - genetics; Retinal Cone Photoreceptor Cells - physiopathology; Retinal Degeneration - genetics; Retinal Degeneration - physiopathology; Retinopathies; RPGR gene; Sequence Deletion; Visual Fields; X Chromosome; X-linked cone dystrophy
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/11.5.605

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.