Abstract
Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the genes encoding rhodopsin, the β subunit of rod phosphodiesterase (PDEB) and, recently, in the gene for rod cGMP-gated channel, have been reported. However, detailed genetic involvement has not been ascertained in the great majority of cases. Recoverin, another member of the light transduction pathway, is a candidate gene for ARRP. We report the first analyses of the involvement of the recoverin gene (RCV1) in 42 Spanish ARRP families. Linkage and homozygosity studies with an intragenic polymorphism and the close markers D17S945 and D17S786 ruled out RCV1 as the cause of ARRP in 38 pedigrees. In the four remaining families, single strand conformation polymorphism analysis of the recoverin-coding region detected no mutations in the parents or in the affected members. These results strongly suggest that mutations in the RCV1 gene are not responsible for ARRP in these families.
Similar content being viewed by others
References
Bayés M, Giordano M, Balcells S, Grinberg D, Vilageliu L, Martínez I, Ayuso C, Benítez J, Ramos-Arroyo MA, Chivelet P, Solans T, Valverde D, Amselem S, Goossens M, Baiget M, Gonzàlez-Duarte R, Besmond C (1995) A homozygous tandem duplication within the gene encoding the beta subunit of rod phosphodiesterase as a cause for autosomal recessive retinitis pigmentosa. Hum Mutat 5: 228–234
Berson EL (1993) Retinitis-pigmentosa — the Friedenwald lecture. Invest Ophthalmol Vis Sci 34: 1659–1676
Boughman JA, Conneally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32: 223–235
Cotran PR, Ringens PJ, Crabb JW, Berson EL, Dryja TP (1990) Analysis of the DNA of patients with retinitis pigmentosa with a cellular retinaldehyde binding protein cDNA. Exp Eye Res 51: 15–19
Cotran PR, Bruns GAP, Berson EL, Dryja TP (1991) Genetic analysis of patients with retinitis pigmentosa using a cloned cDNA probe for the human gamma subunit of cyclic GMP phosphodiesterase. Exp Eye Res 53: 557–564
Dizhoor AM, Ray S, Kumar S, Niemi G, Spencer M, Brolley D, Walsh KA, Philipov PP, Hurley JB, Stryer L (1991) Recoverin: a calcium sensitive activator of retinal rod guanylate cyclase. Science 251: 915–918
Dollfus H, Rozet J-M, Musarella MA, Kaplan J, Munnich A (1993) Dinucleotide repeat polymorphism at the human recoverin RCVI gene locus on chromosome 17p. Hum Mol Genet 2: 1081
Dryja TP (1990) Deficiencies in sight with the candidate gene approach. Nature 347: 614
Greenberg J, Goliath R, Beighton P, Ramesar R (1994) A new locus for autosomal dominant retinitis pigmentosa on the short arm of chromosome 17. Hum Mol Genet 3: 915–918
Hahn LB, Berson EL, Dryja TP (1994) Evaluation of the gene encoding the gamma subunit of rod phosphodiesterase in retinitis pigmentosa. Invest Ophthalmol Vis Sci 35: 1077–1082
Heckenlively JR, Yoser SL, Friedman LH, Oversier JJ (1988) Clinical findings and common symptoms in retinitis pigmentosa. Am J Ophthalmol 105: 504–511
Humphries P, Farrar JG, Keena P, McWilliam P (1990) Retinitis pigmentosa: genetic mapping in X-linked and autosomal forms of the disease. Clin Genet 38: 1–13
Hurley JB, Dizhoor AM (1993) Recoverin's role: conclusion withdrawn. Science 260: 740
Kajiwara K, Berson EL, Dryja TP (1994) Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science 264: 1604–1608
Kumaramanickavel G, Maw M, Denton MJ, John S, Srikumari CRS, Orth U, Oehlmann R, Gal A (1994) Missense rhodopsin mutation in a family with recessive RP. Nature Genet 8: 10–11
Lander ES, Botstein D (1987) Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236: 1567–1568
Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81: 3443–3446
McGee TL, Lin D, Berson EL, Dryja TP (1994) Defects in the rod cGMP-gated channel gene in patients with retinitis pigmentosa. Invest Ophtalmol Vis Sci 35: 1716
McLaughlin ME, Sabdberg MA, Berson EL, Dryja TP (1993) Recessive mutations in the gene encoding the β-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nature Genet 4: 130–133
Miller SA, Dyke DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215
Murakami A, Yajima T, Inana G (1992) Isolation of human retinal genes recoverin cDNA and gene. Biochem Biophys Res Commun 187: 234–244
O'Connell P, Plaetke R, Matsunami N, Odelberg S, Jorde L, Chance P, Leppert M, Laiouel JM, White R (1993) An extended genetic linkage map and an index map for human chromosome-17. Genomics 15: 38–47
Oliveira L, Miniou P, Viegaspequignot E, Rozet JM, Dollfus H, Pittler SJ (1994) Human retinal guanylate cyclase (GUC2D) maps to chromosome 17pl3.1. Genomics 22: 478–481
Ringens PJ, Fang M, Shinahara T, Bridges CD, Lerea CL, Berson EL, Dryja TP (1990) Analysis of gene coding for S-antigen, interstitial retinol binding protein, and the alpha-subunit of cone transducin in patients with retinitis pigmentosa. Invest Ophthalmol Vis Sci 31: 1421–1426
Rosenfeld PJ, Cowley GS, McGee TL, Sandberg MA, Berson EL, Dryja TP (1992) A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa. Nature Genet 1: 209–213
Sheffield VC, Beck J, Kwitek AE, Sandstrom DW, Stone EM (1993) The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions. Genomics 16: 325–332
Tombran-Tink J, Pawar H, Swaroop A, Rodriguez I, Chader GJ (1994) Localization of the gene for pigment epithelium-derived factor (PDEF) to chromosome 17p13.1 and expression in cultured human retinoblastoma cells. Genomics 19: 266–272
Weissenbach J, Gyapay G. Dib C, Vignal A, Morissette J, Millasseau P, Vaysseix G, Lathrop M (1992) A second-generation linkage map of the human genome. Nature 359: 794–801
Wiechmann AF, Akots G, Hammarback JA, Pettenati MJ, Rao PN, Bowden DW (1994a) Genetic and physical mapping of human recoverin a gene expressed in retinal photoreceptors. Invest Ophthalmol Vis Sci 35: 325–331
Wiechmann AF, Haro KC, Bowden DW (1994b) Three microsatellite polymorphisms at the recoverin locus on chromosome 17. Hum Mol Genet 3: 1028
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bayés, M., Valverde, D., Balcells, S. et al. Evidence against involvement of recoverin in autosomal recessive retinitis pigmentosa in 42 Spanish families. Hum Genet 96, 89–94 (1995). https://doi.org/10.1007/BF00214192
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00214192