RESUMO
In the present study, we screened 529 Brazilian individuals affected by inherited retinal disorders. A total of seven unrelated and nonsyndromic patients with RP1 biallelic variants (OMIM # 180100) were diagnosed in our centre and included in the study. They had classic retinitis pigmentosa with diagnosis at the first decade of life. The visual acuities were severely affected at a young age. The fundus aspects were similar among all patients. An atrophic ring was present around the fovea in several cases. All patients had molecular diagnosis, with six different RP1 variants. This study reports two new pathogenic variants - two frameshift duplications (c.1234dupA p.Met412Asnfs*7 and c.1265dupC p.Ala423Cysfs*2) and reinforces other four known pathogenic variants - two frameshift deletions (c.469delG p.Val157Trpfs*16 and c.3843delT p.Pro1282Leufs*12) and two stop gain mutations (c.1186 C > T p.Arg396* and c.1625C > G p.Ser542*). These findings broaden the spectrum of RP1 variants. This study also reviewed the fundus characteristics that clinically could raise the hypothesis of a retinitis pigmentosa due to RP1 gene. It is worthwhile to try to identify the disease-causing variants in each patient since it can provide prognostic information and be useful in genetic consultation and diagnosis in the future.
Assuntos
Proteínas Associadas aos Microtúbulos/genética , Mutação/genética , Retinose Pigmentar/genética , Adolescente , Adulto , Alelos , Brasil , Proteínas do Olho/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Prognóstico , Retina/patologia , Estudos Retrospectivos , Acuidade Visual/genética , Adulto JovemRESUMO
PURPOSE: To analyze risk factors for recurrent toxoplasmic retinochoroiditis. DESIGN: Single center prospective case series. POPULATION AND METHODS: A total of 230 patients with toxoplasmic retinochoroiditis were prospectively followed to assess recurrences. All patients were treated with a specific drug regime for toxoplasmosis in each episode of active retinochoroiditis. Individuals with chronic diseases and pregnant women were excluded. Survival analysis by extended Cox regression model (Prentice-Williams-Peterson counting process model) was performed to evaluate the time between recurrences according to some potential risk factors: age, number of retinochoroidal lesions at initial evaluation, sex and interferon gamma +874 T/A gene polymorphism. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided to interpret the risk effects. RESULTS: One hundred sixty-two recurrence episodes were observed in 104 (45.2%) patients during follow-up that lasted from 269 to 1976 days. Mean age at presentation was 32.8 years (Standard deviation = 11.38). The risk of recurrence during follow up was influenced by age (HR = 1.02, 95% CI = 1.01-1.04) and number of retinochoroidal lesions at the beginning of the study (HR = 1.60, 95% CI = 1.07-2.40). Heterozygosis for IFN-γ gene polymorphism at position +874 T/A was also associated with recurrence (HR = 1.49, 95% CI = 1.04-2.14). CONCLUSION: The risk of ocular toxoplasmosis recurrence after an active episode increased with age and was significantly higher in individuals with primary lesions, which suggests that individuals with this characteristic and the elderly could benefit from recurrence prophylactic strategies with antimicrobials. Results suggest an association between IFN-γ gene polymorphism at position +874T/A and recurrence.
Assuntos
Coriorretinite/genética , Interferon gama/genética , Polimorfismo Genético/genética , Toxoplasmose Ocular/genética , Adolescente , Anti-Infecciosos/uso terapêutico , Coriorretinite/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Prospectivos , Recidiva , Fatores de Risco , Análise de Sobrevida , Toxoplasmose Ocular/tratamento farmacológico , Acuidade Visual/genéticaRESUMO
Choroideremia is an X-linked recessive retinal dystrophy characterized by progressive loss of the photoreceptor, the retinal pigment epithelium, and the choriocapillaris layers which ultimately can result in blindness by the fifth decade of life. The disease is caused by mutations in the gene CHM, which encodes a protein involved in the regulation of intracellular vesicular traffic. Typically, hemizygous males are affected by the disease and female carriers are asymptomatic with only a diffuse mottled pattern of hyperpigmentation on funduscopy. Uncommon instances of fully affected females have been described previously and these cases are proposed to arise from an skewed Lyonization mechanism preferentially inactivating the X chromosome carrying the normal CHM allele. In this work, the clinical and molecular features of two Mexican families with choroideremia are described. A novel and a previously described CHM mutation were identified. X-chromosome inactivation assays were performed in a total of 12 heterozygous carriers from the two families. In an affected female from family A, a random X-inactivation pattern was demonstrated; on the other hand, in a female carrier from family B displaying a conspicuous pattern of pigment epithelium mottling at the peripheral retina, a skewed X-inactivation pattern was found. However, the X-chromosome preferentially inactivated in this female was the one carrying the mutated allele. Our results add to the genotypic spectrum in choroideremia and does not support a correlation between X-inactivation status and abnormal retinal phenotype in heterozygous female carriers from these two families.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Coroideremia/genética , Inativação do Cromossomo X/fisiologia , Adulto , Idoso , Criança , Análise Mutacional de DNA , Eletrorretinografia , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Acuidade Visual/genética , Inativação do Cromossomo X/genética , Adulto JovemRESUMO
Este trabalho apresenta 5 casos de pacientes com associaçäo de malformaçöes oculares composta por coloboma, microftalmo e microcórnea. Os autores tentam estabelecer o diagnóstico genético em cada caso e apresentam os procedimentos oftalmológicos realizados no sentido de minmizar o déficit visual decorrente destas alteraçöes. Discute-se também as indicaçöes e as dificuldades encontradas para a realizaçäo destes procedimentos. Houve melhora da acuidade visual em todos os casos cirúrgicos