RESUMEN
Mutations in more than 60 different genes have been associated with non-syndromic and syndromic retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies. To increase the understanding of the molecular epidemiology of the disease in Italy, we analyzed 56 patients with syndromic and non-syndromic forms of RP attending the Retinitis Pigmentosa Center of San Paolo Hospital (Milan, Italy). Patients underwent detailed clinical examination. Genomic DNA isolated from peripheral blood samples was screened for mutations in different genes according to RP form by direct sequencing analysis. The impact of novel missense mutations on protein functions was predicted by in silico analysis and protein sequence alignment. Cosegregation analysis was performed between available family members. Forty-one of the 56 probands analyzed had non-syndromic and 15 had syndromic RP forms. Putative disease-causing mutations were identified in 19 of 56 unrelated RP probands. Mutation screening identified a total of 22 different heterozygous variants. Notably, 12 of these putative pathogenic mutations have not been previously reported. New variants were found to be located on the USH2A, RPGR, EYS, and RHO genes. All 3 new variants detected in X-linked RP probands were confirmed in other affected family members. We found a positivity rate of 24.4% and 60% for probands with non-syndromic and syndromic RP, respectively. This is the first report of RPGR X-linked RP proband-ORF15 mutations in Italian patients with X-linked (XL)-RP. In addition, this is the first report of data regarding the association between EYS mutations and non-syndromic RP forms in the Italian population.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Mutación , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/patología , Adulto , Anciano , Secuencia de Aminoácidos , Secuencia de Bases , Análisis Mutacional de ADN , Proteínas de la Matriz Extracelular/genética , Proteínas del Ojo/genética , Salud de la Familia , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Rodopsina/genética , Homología de Secuencia de Aminoácido , Síndrome , Adulto JovenRESUMEN
PURPOSE: To report the molecular characterization of a novel VMD2 mutation causing a Best macular dystrophy sporadic case. METHODS: All family members underwent ophthalmologic examination and genetic testing by single strand conformation polymorphism analysis and direct sequencing of the VMD2 gene. RESULTS: A single T to G transition at nucleotide 663 was identified in one of the VMD2 gene copies of the patient, which results in a Cys to Trp substitution at position 221 in the corresponding protein (C221W). Sequence analysis of the VMD2 exon 6 of both parents of the patient did not reveal any mutation. CONCLUSION: These data confirm the involvement of the VMD2 gene in Best macular dystrophy onset, even in sporadic cases of the disease, pointing out the relevance of molecular analysis in the diagnosis of this degenerative retinal disease.