RESUMO
This report describes ocular findings obtained in four patients from three families with autosomal dominant retinitis pigmentosa (adRP) due to missense mutations in the rhodopsin gene. Phenotypes were characterized by standard ophthalmologic examinations, visual fields, electroretinography (ERG), dark adaptation, and two-color dark-adapted threshold perimetry. Two patients aged 38 and 45 years, respectively, from a family with the Cys110Phe mutation showed mild fundus changes without bone spicules as well as small arcuate scotomas in the inferior quadrants of their visual fields but displayed severe functional loss of rods and cones in the ERG. Two-color dark-adapted threshold perimetry revealed a regional type of degeneration. A 48-year-old patient with an Arg135Gly mutation had typical RP with concentrically narrowed visual fields and nondetectable ERG responses. Central visual functions were well preserved for a long time. Two-color dark-adapted threshold perimetry indicated a diffuse type of retinal degeneration. An 18-year-old patient with a Gln344stop mutation has been followed for 13 years. His ERG was clearly reduced at the age of 5 years; since that time, disease progression has been very slow. Currently, there are relatively mild alterations in visual acuity, rod sensitivity, and visual fields. Our findings confirm that there is a large phenotypic variety among patients with adRP and different rhodopsin mutations.
Assuntos
Mutação Puntual/genética , Retinose Pigmentar/genética , Rodopsina/genética , Adolescente , Adulto , Criança , Pré-Escolar , Adaptação à Escuridão , Progressão da Doença , Eletrorretinografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Células Fotorreceptoras/fisiopatologia , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Retinose Pigmentar/fisiopatologia , Testes de Campo Visual , Campos VisuaisRESUMO
Reliable sex determination is an inevitable prerequisite in prenatal and preimplantation diagnosis of X-linked diseases. We report on an amelogenin-based nested polymerase chain reaction sexing method that simultaneously amplifies distinguishable fragments from both sex chromosomes. Primers matching a largely homologous region on both sex chromosomes are used that encompass a 177-bp deletion on the Y chromosome. Thus amplification results in X- and Y-specific fragments of different sizes that are resolved simply by agarose gel electrophoresis. We applied our sexing strategy to 102 single amniocytes previously subjected to primer extension preamplification. 95 showed successful amplification (93.14% sensitivity). The genotyping of all successful amplifications (from 42 male and 53 female amniocytes) was found to be correct (100% specificity). None of the media blanks showed amplification products (no false positives). Additional amplification of the locus of the most common cystic fibrosis mutation resulted in 95.1% success: 89 amniocytes (87.3%) showed no mutated allele and 7 (6.9%) were found to be heterozygous for the delta F508 mutation.
Assuntos
Fibrose Cística/diagnóstico , Fibrose Cística/genética , Reação em Cadeia da Polimerase/métodos , Diagnóstico Pré-Natal/métodos , Análise para Determinação do Sexo/métodos , Amelogenina , Amniocentese , Âmnio/citologia , Sequência de Bases , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Primers do DNA/genética , Proteínas do Esmalte Dentário/genética , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Gravidez , Pseudogenes , Cromossomo X/genética , Cromossomo Y/genéticaRESUMO
Two autosomal dominant retinitis pigmentosa families of different origin were screened for rhodopsin mutations using the method of single strand conformation polymorphism and direct sequencing. We found a CGG-CAG substitution in codon 114 of rhodopsin in both families. This change predicted the replacement of a glycine by an aspartic acid and suggested that this change is the cause of the disease in these families.
Assuntos
Ácido Aspártico , Glicina , Mutação Puntual , Retinose Pigmentar/genética , Rodopsina/genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Códon/genética , Feminino , Genes Dominantes , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Polimorfismo GenéticoRESUMO
Clinical phenotypes of patients with mutations in the human RDS/peripherin gene are described. A 67-year-old woman, who carried a 1 base pair deletion in codon 307, presented with typical late onset autosomal dominant retinitis pigmentosa (RP). In another autosomal dominant pedigree, a nonsense mutation at codon 46 caused 'inverse' retinitis pigmentosa-like fundus changes associated with progressive cone-rod degeneration in a 58-year-old man, whereas his 40-year-old son presented with yellow deposits in the retinal pigment epithelial layer resembling a pattern dystrophy, and with moderately reduced rod and cone function, as determined by two colour dark adapted threshold perimetry and electroretinography. It is suggested that both clinical pictures within this latter family may represent manifestations of fundus flavimaculatus. The clinical data of the three patients provide further evidence for the remarkable variety of disease expression within and between families with mutations in the RDS/peripherin gene. Currently, the most comprehensive statement could be that RDS/peripherin mutations are associated either with typical RP or with various forms of flecked retinal disease.
Assuntos
Deleção Cromossômica , Proteínas de Filamentos Intermediários/genética , Glicoproteínas de Membrana , Proteínas do Tecido Nervoso , Degeneração Retiniana/genética , Adulto , Idoso , Percepção de Cores/fisiologia , Feminino , Fundo de Olho , Genes Dominantes , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neuropeptídeos/genética , Linhagem , Periferinas , Fenótipo , Degeneração Retiniana/fisiopatologia , Limiar Sensorial/fisiologia , Campos VisuaisAssuntos
Transportadores de Cassetes de Ligação de ATP/genética , Adrenoleucodistrofia/genética , Proteínas de Membrana/genética , Mutação Puntual , Cromossomo X , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP , Sequência de Aminoácidos , Sequência de Bases , Códon/genética , Sequência Conservada , Primers do DNA , Éxons , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , Mapeamento por RestriçãoAssuntos
Cegueira/genética , Anormalidades do Olho/genética , Mutação Puntual , Cromossomo X , Sequência de Aminoácidos , Sequência de Bases , Cegueira/epidemiologia , Cuba/epidemiologia , Surdez/epidemiologia , Surdez/genética , Éxons , Anormalidades do Olho/epidemiologia , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/genética , Masculino , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , SíndromeRESUMO
Eighty-eight patients/families with autosomal dominant retinitis pigmentosa (RP) were screened for rhodopsin mutations. Direct sequencing revealed 13 different mutations in a total of 14 (i.e., 16%) unrelated patients. Five of these mutations (T4K, Q28H, R135G, F220C, and C222R) have not been reported so far. In addition, multipoint linkage analysis was performed on two large families with autosomal dominant RP due to rhodopsin mutations by using five DNA probes from 3q21-q24. No tight linkage was found between the rhodopsin locus (RHO) and D3S47 (theta max = 0.08). By six-point analysis, RHO was localized in the region between D3S21 and D3S47, with a maximum lod score of 13.447 directly at D3S20.
