Mutations in C2ORF71 cause autosomal-recessive retinitis pigmentosa.
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.
Collin
Rob W J
RW
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Safieh
Christine
C
Littink
Karin W
KW
Shalev
Stavit A
SA
Garzozi
Hanna J
HJ
Rizel
Leah
L
Abbasi
Anan H
AH
Cremers
Frans P M
FP
den Hollander
Anneke I
AI
Klevering
B Jeroen
BJ
Ben-Yosef
Tamar
T
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
D005136:Eye Proteins; C550125:PCARE protein, human; D011506:Proteins
Methods Mol Biol. 2000;132:365-86
10547847
Acta Ophthalmol (Copenh). 1973;51(4):445-60
4543597
Nature. 1979 Oct 18;281(5732):602-3
492326
Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5431-8
18055789
Am J Hum Genet. 2008 Nov;83(5):594-603
18976725
Mol Vis. 2008 Apr 21;14:675-82
18432314
Lancet. 2006 Nov 18;368(9549):1795-809
17113430
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13726-30
8943002