Assuntos
Neovascularização de Coroide/patologia , Proteínas de Filamentos Intermediários/genética , Glicoproteínas de Membrana/genética , Mutação , Proteínas do Tecido Nervoso/genética , Degeneração Retiniana/genética , Vasos Retinianos/metabolismo , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/complicações , Feminino , Deleção de Genes , Humanos , Pessoa de Meia-Idade , Periferinas , Degeneração Retiniana/complicações , Degeneração Retiniana/diagnósticoRESUMO
PURPOSE: To describe a novel mutation in the RDS/Peripherin gene that results in a moderately severe form of adult-onset foveomacular dystrophy. DESIGN: Observational case series. METHODS: Selected members of a family with adult-onset foveomacular dystrophy underwent complete ophthalmic evaluation, including fundus photography and fluorescein angiography, in a tertiary care referral center. The study population consisted of 12 members of a Caucasian kindred. After providing informed consent, patients donated blood for genomic DNA extraction and mutational screening using standard techniques. The main outcome measure were the presence of a RDS/Peripherin gene mutation in a patient with the disease and its absence in unaffected family members and controls. RESULTS: Eight affected family members and no unaffected family members demonstrated a single guanine base deletion at nucleotide 112 that led to premature termination at amino acid 38 of RDS/Peripherin polypeptide. This frameshift mutation results in truncation of nearly 90% of the gene product, thus probably representing a null allele. That results in a relatively severe phenotype, with choroidal neovascularization developing in two patients and geographic atrophy involving the macula in three patients. CONCLUSIONS: We describe a frameshift null mutation in the RDS/Peripherin gene associated with a relatively severe manifestation of adult-onset foveomacular dystrophy in affected family members.
Assuntos
Proteínas do Olho/genética , Mutação da Fase de Leitura , Proteínas de Filamentos Intermediários/genética , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso/genética , Degeneração Retiniana/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Criança , DNA/análise , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Periferinas , Degeneração Retiniana/diagnóstico , Deleção de SequênciaRESUMO
X-linked cone dystrophy is a type of hereditary retinal degeneration characterized by a progressive dysfunction of the day vision or photopic (cone) system with preservation of night vision or scotopic (rod) function. The disease presents with a triad of photophobia, loss of color vision and reduced central vision. This phenotype is distinct from retinitis pigmentosa (RP) in which there are prominent night and peripheral vision disturbances. X-linked cone dystrophy is a genetically heterogeneous disorder, with linkage to loci on Xp11.4--Xp21.1 (COD1, OMIM 304020) and Xq27 (COD2, OMIM 303800). COD1 maps to a region that harbors the RPGR gene, mutations in which account for >70% of patients with X-linked RP. The majority of these mutations reside in one purine-rich exon, ORF15, encoding 567 amino acids with a repetitive domain rich in glutamic acid residues. We mapped two families with X-linked cone dystrophy to the COD1 locus and identified two distinct mutations in ORF15 in the RPGR gene (ORF15+1343_1344delGG and ORF15+694_708del15) leading to a frame-shift and premature termination of translation in one case and a deletion of five amino acids in another. Consistent with expression of RPGR in rods and cones, our results show that mutations in RPGR, in addition to X-linked RP, can also cause cone-specific degeneration.