RESUMO
PURPOSE: The X-linked form of retinitis pigmentosa (XLRP) is the most severe type because of its early onset and rapid progression. Five XLRP loci have been mapped, although only two genes, RPGR (for RP3) and RP2, have been cloned. In this study, 30 unrelated XLRP Spanish families were screened to determine the molecular cause of the disease. METHODS: Haplotype analysis was performed, to determine whether the disease is linked to the RP3 or RP2 region. In those families in which the disease cosegregates with either locus, mutational screening was performed. The RP2 gene, the first 15 exons of RPGR at the cDNA level, and the open reading frame (ORF) 14 and 15 exons were screened at the genomic DNA level. RESULTS: Haplotype analysis ruled out the implication in the disease of RP2 in six families and of RPGR in four families. Among the 30 unrelated XLRP families, there 4 mutations were identified in RP2 (13%), 3 of which are novel, and 16 mutations in RPGR (53.3%), 7 of which are novel. CONCLUSIONS: In this cohort of XLRP families, as has happened in previous studies, RP3 also seems to be the most prevalent form of XLRP, and, based on the results, the authors propose a four-step protocol for molecular diagnosis of XLRP families.
Assuntos
Proteínas do Olho/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Mutação , Retinose Pigmentar/genética , Análise Mutacional de DNA , Feminino , Proteínas de Ligação ao GTP , Haplótipos , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , EspanhaRESUMO
PURPOSE: Secreted Frizzled Related Proteins (SFRPs) are soluble molecules capable of modulating Wnt signalling. Different lines of evidence indicate that SFRP activity is related with the development and function of the retina photoreceptor cells as well as with their apoptotic degeneration associated with the onset of different cases of retinal dystrophy (RD). Because the genetic causes of many retinal dystrophies still need to be determined, we have asked whether mutations in the SFRP genes might be associated with retinal dystrophies. METHODS: Here we describe the genomic structure of SFRP1, SFRP2, and SFRP5 and a mutational screening of SFRP1 in 325 individuals affected by various non X-linked forms of inherited retinal disorders. RESULTS: Three polymorphic variants were identified. CONCLUSIONS: Our data, so far, exclude SFRP1 as a molecular cause of RD, since two out of three genetic variants of the gene were present in both RD patients and normal population.