Navegando por Palavras-chave "Stargardt disease"

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    Correlação entre fenótipo e genótipo de pacientes com doença de Stargardt
    (Universidade Federal de São Paulo (UNIFESP), 2018-08-30) Salles, Mariana Vallim [UNIFESP]; Sallum, Juliana Maria Ferraz [UNIFESP]; http://lattes.cnpq.br/0856630824759511; Pesquero, João Bosco; http://lattes.cnpq.br/2233267084488852; http://lattes.cnpq.br/6434715002327011; Universidade Federal de São Paulo (UNIFESP)
    Purpose: To identify genetic variants in Brazilian patients with clinical diagnosis of Stargardt disease and to correlate with its phenotypic manifestation and hereditary characteristics. Methods: Patients with clinical diagnosis of Stargardt disease from retina clinic of UNIFESP were included. Medical records from patients from the Instituto de Genética Ocular, São Paulo – Brazil, were reviewed. The ABCA4, ELOVL4 and PROM1 genes were analyzed by the nextgeneration sequencing (NGS) and complementation with the Sanger sequencing. Results: 52 patients from 47 families were included. In the first phase 24 patients from 21 families from retina clinic of UNIFESP were selected. In the second phase, 254 medical records from Instituto de Genética Ocular were reviewed. Of these, 28 patients from 26 families with pathogenic variants in the ABCA4 and PROM1 genes detected by NGS were selected. No patient had genetic alteration in the ELOVL4 gene. The age of the patients varied from 10 to 66 years and the age of onset of symptoms was on average 14 years of age (ranged from 5 to 40 years of age). A visual acuity ranged from 20/40 to 20 cm at the time of examination. Retinal flecks was found in the retina examination and was associated with macular atrophy. The ABCA4 gene sequencing was conclusive in 41 patients, inconclusive in 8 and negative in 1 case. Two patients have their phenotypic characteristics due to the presence of variants in the PROM1 gene. This study described 5 new pathogenic variants and 3 new complex alleles in the ABCA4 gene. Conclusion: The NGS gene panel was effective to conclude the diagnosis in approximately 80% of the patients. Despite wide genetic and clinic variability, there was concordance in sibling disease expression with the same genotype. The identification of the complex alleles in 14 families (30% of cases) reinforces the importance of the segregation test for the conclusion of the molecular diagnosis related to the ABCA4 gene.
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    Novel Complex ABCA4 Alleles in Brazilian Patients With Stargardt Disease: Genotype-Phenotype Correlation
    (Assoc Research Vision Ophthalmology Inc, 2017) Salles, Mariana Vallim [UNIFESP]; Motta, Fabiana Louise [UNIFESP]; da Silva, Elton Dias [UNIFESP]; Varela, Patricia [UNIFESP]; Costa, Karita Antunes; Filippelli-Silva, Rafael [UNIFESP]; Martin, Renan Paulo [UNIFESP]; Chiang, John (Pei-Wen); Pesquero, Joao Bosco [UNIFESP]; Ferraz Sallum, Juliana Maria [UNIFESP]
    PURPOSE. To analyze the presence of complex alleles of the ABCA4 gene in Brazilian patients with Stargardt disease and to assess the correlation with clinical features. METHODS. This was an observational cross-sectional study. Patients with a diagnosis of Stargardt disease who presented three pathogenic variants of the ABCA4 gene or who had variants previously described as complex alleles were included. The relatives of these probands were evaluated in the segregation analysis. The patients were evaluated based on age at symptom onset and visual acuity, and the clinical characteristics were classified according to the findings observed on autofluorescence examination. RESULTS. Among the 47 families analyzed, approximately 30% (14/47) presented complex alleles. The segregation analysis in 14 families with cases of Stargardt disease identified three novel complex alleles and one previously described complex allele. The known complex allele p.[Leu541Pro; Ala1038Val] was identified in two families. The novel complex alleles identified were p.[Leu541Pro; Arg1443His] in five families, p.[Ser1642Arg; Val1682 Val1686-dell in seven families, and p. [Pro1761Arg; Arg2106Cys] in one family. Furthermore, four new variants (p.Lys22Asn, p.Asp915Asn, p. Glu1447Val, and p. Pro1761Arg) were identified in the second allele of the ABCA4 gene. CONCLUSIONS. Segregation analysis is important in order to confirm the molecular diagnosis of patients with Stargardt disease, given the frequency of complex alleles in the ABCA4 gene. The various pathogenic variation combinations observed in this study were associated with different phenotypes.