title: Mutations in C2ORF71 cause autosomal-recessive retinitis pigmentosa.
abstract: With a worldwide prevalence of 1 in 4,000, retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration. More than 30 genes and loci have been implicated in nonsyndromic autosomal-recessive (ar) RP. Genome-wide homozygosity mapping was conducted in one Dutch and one Israeli family affected by arRP. The families were found to share a 5.9 Mb homozygous region on chromosome 2p23.1-p23.3. A missense variant in one of the genes residing in this interval, C2ORF71, has recently been reported to be associated with RP. C2ORF71, encoding a putative protein of 1,288 amino acids, was found to be specifically expressed in human retina. Furthermore, RT-PCR analysis revealed that in the mouse eye, C2orf71 is expressed as early as embryonic day 14. Mutation analysis detected a 1 bp deletion (c.946 del; p.Asn237MetfsX5) segregating with RP in the Dutch family, whereas a nonsense mutation (c.556C > T; p.Gln186X) was identified in the Israeli family. Microsatellite-marker analysis in additional Israeli families revealed cosegregation of a C2ORF71-linked haplotype in one other family, in which a 13 bp deletion (c.2756_2768 del; p.Lys919ThrfsX) was identified. Clinically, patients with mutations in C2ORF71 show signs of typical RP; these signs include poor night vision and peripheral field loss, typical retinal bone-spicule-type pigment deposits, pale appearance of the optic disk, and markedly reduced or completely extinguished electroretinograms. In conclusion, truncating mutations in C2ORF71 were identified in three unrelated families, thereby confirming the involvement of this gene in the etiology of arRP.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Christine
authors.initials: C
authors.lastname: Safieh
authors.forename: Karin W
authors.initials: KW
authors.lastname: Littink
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
authors.forename: Hanna J
authors.initials: HJ
authors.lastname: Garzozi
authors.forename: Leah
authors.initials: L
authors.lastname: Rizel
authors.forename: Anan H
authors.initials: AH
authors.lastname: Abbasi
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yosef
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D051379:Mice; D018895:Microsatellite Repeats; D009154:Mutation; D020125:Mutation, Missense; D011506:Proteins / Q000235:genetics*; D012160:Retina / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005136:Eye Proteins; C550125:PCARE protein, human; D011506:Proteins
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