TY - JOUR
T1 - Variants in the ABCA4 gene in a Brazilian population with stargardt disease
AU - Salles, Mariana Vallim
AU - Motta, Fabiana Louise
AU - Martin, Renan
AU - Filippelli-Silva, Rafael
AU - da Silva, Elton Dias
AU - Varela, Patricia
AU - Costa, Kárita Antunes
AU - Chiang, John Peiwen
AU - Pesquero, João Bosco
AU - Sallum, Juliana Maria Ferraz
N1 - Funding Information:
This research was supported by research funds from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; Process No. 2012/50454-5). The authors are grateful for fellowship support from CAPES (FLM, MVS and KAC), CNPq (RFS) and FAPESP (RPM). The authors sincerely appreciate the help provided by R. Allikmets during the analysis of the results. DECLARATION OF INTERESTS: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. Despite the similarity in names, Molecular Vision Laboratory is not related to the journal, Molecular Vision. The Molecular Vision Laboratory, Inc., is a medical diagnostic laboratory and subsidiary of Centrillion Technology Holdings Ltd. There are no financial or intellectual relationships to be disclosed.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Purpose: The aim of this study was to analyze and report pathogenic variants in the ABCA4 gene in Brazilian patients with a clinical diagnosis of Stargardt disease. Methods: This retrospective study evaluated variants in the ABCA4 gene in Brazilian patients with Stargardt disease. The patients’ visual acuity and age of symptom onset were obtained from previous medical records. The patients were classified according to the autofluorescence patterns. Results: Fifty patients aged between 10 and 65 years from 44 families were included in the study. Among these cases, the mean age of symptom onset was 14 years (range, 5–40 years). ABCA4 gene sequencing was conclusive in 40 patients (80%), negative in two patients (4%), and inconclusive in eight patients (16%). Four families carried homozygous pathogenic variants. Segregation analysis results were available for 23 families. One novel variant was found: p.Ala2084Pro. The most frequent pathogenic variant in this group was p.Arg602Trp (12/100 alleles). Based on the phenotypic characteristics assessed with fundus autofluorescence imaging, 12 patients were classified as having type I phenotype, 16 as having type II, and 18 patients as having type III. The cases classified as type III phenotype included patients who were homozygous for the p.Asn96Asp and p.Arg2030* variants. One patient with a type I phenotype carried the homozygous intronic variant c.3862+1G>A. Conclusions: Next-generation sequencing was effective for the molecular diagnosis of genetic diseases and specifically allowed a conclusive diagnosis in 80% (40/50) of the patients. As the ABCA4 gene does not show a preferential region for pathogenic variants, the diagnosis of Stargardt disease depends on broader analysis of the gene. The most common pathogenic variants in the ABCA4 gene described in the literature were also found in these Brazilian patients. Although some genotype–phenotype correlations were found, more studies regarding the progression of Stargardt disease will help increase our understanding of the pathogenicity of these gene variants.
AB - Purpose: The aim of this study was to analyze and report pathogenic variants in the ABCA4 gene in Brazilian patients with a clinical diagnosis of Stargardt disease. Methods: This retrospective study evaluated variants in the ABCA4 gene in Brazilian patients with Stargardt disease. The patients’ visual acuity and age of symptom onset were obtained from previous medical records. The patients were classified according to the autofluorescence patterns. Results: Fifty patients aged between 10 and 65 years from 44 families were included in the study. Among these cases, the mean age of symptom onset was 14 years (range, 5–40 years). ABCA4 gene sequencing was conclusive in 40 patients (80%), negative in two patients (4%), and inconclusive in eight patients (16%). Four families carried homozygous pathogenic variants. Segregation analysis results were available for 23 families. One novel variant was found: p.Ala2084Pro. The most frequent pathogenic variant in this group was p.Arg602Trp (12/100 alleles). Based on the phenotypic characteristics assessed with fundus autofluorescence imaging, 12 patients were classified as having type I phenotype, 16 as having type II, and 18 patients as having type III. The cases classified as type III phenotype included patients who were homozygous for the p.Asn96Asp and p.Arg2030* variants. One patient with a type I phenotype carried the homozygous intronic variant c.3862+1G>A. Conclusions: Next-generation sequencing was effective for the molecular diagnosis of genetic diseases and specifically allowed a conclusive diagnosis in 80% (40/50) of the patients. As the ABCA4 gene does not show a preferential region for pathogenic variants, the diagnosis of Stargardt disease depends on broader analysis of the gene. The most common pathogenic variants in the ABCA4 gene described in the literature were also found in these Brazilian patients. Although some genotype–phenotype correlations were found, more studies regarding the progression of Stargardt disease will help increase our understanding of the pathogenicity of these gene variants.
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M3 - Article
C2 - 30093795
AN - SCOPUS:85051683548
VL - 24
SP - 546
EP - 559
JO - Molecular Vision
JF - Molecular Vision
SN - 1090-0535
ER -