Novel Complex ABCA4 Alleles in Brazilian Patients With Stargardt Disease: Genotype-Phenotype Correlation

Novel Complex ABCA4 Alleles in Brazilian Patients With Stargardt Disease: Genotype-Phenotype Correlation

Author Salles, Mariana Vallim Autor UNIFESP Google Scholar
Motta, Fabiana Louise Autor UNIFESP Google Scholar
da Silva, Elton Dias Autor UNIFESP Google Scholar
Varela, Patricia Autor UNIFESP Google Scholar
Costa, Karita Antunes Google Scholar
Filippelli-Silva, Rafael Autor UNIFESP Google Scholar
Martin, Renan Paulo Autor UNIFESP Google Scholar
Chiang, John (Pei-Wen) Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Ferraz Sallum, Juliana Maria Autor UNIFESP Google Scholar
Abstract 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.
Keywords Stargardt disease
macular degeneration/genetics
retinal dystrophy
eye diseases
ABCA4 protein
complex allele
xmlui.dri2xhtml.METS-1.0.item-coverage Rockville
Language English
Sponsor Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Grant number FAPESP: 2012/50454-5
Date 2017
Published in Investigative Ophthalmology & Visual Science. Rockville, v. 58, n. 13, p. 5715-5722, 2017.
ISSN 0146-0404 (Sherpa/Romeo, impact factor)
Publisher Assoc Research Vision Ophthalmology Inc
Extent 5715-5722
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000419071600013

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