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Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles

AIM: To evaluate the frequency and pattern of disease-associated mutations of ABCA4 gene among Greek patients with presumed Stargardt disease (STGD1). MATERIALS AND METHODS: A total of 59 patients were analyzed for ABCA4 mutations using the ABCR400 microarray and PCR-based sequencing of all coding e...

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Autores principales: Smaragda, Kamakari, Vassiliki, Kokkinou, George, Koutsodontis, Polixeni, Stamatiou, Christoforos, Giatzakis, Anastasios, Anastasakis, Minas, Aslanides Ioannis, Stavrenia, Koukoula, Theoni, Panagiotoglou, Ioannis, Datseris, Miltiadis, Tsilimbaris K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952432/
https://www.ncbi.nlm.nih.gov/pubmed/29854428
http://dx.doi.org/10.1155/2018/5706142
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author Smaragda, Kamakari
Vassiliki, Kokkinou
George, Koutsodontis
Polixeni, Stamatiou
Christoforos, Giatzakis
Anastasios, Anastasakis
Minas, Aslanides Ioannis
Stavrenia, Koukoula
Theoni, Panagiotoglou
Ioannis, Datseris
Miltiadis, Tsilimbaris K.
author_facet Smaragda, Kamakari
Vassiliki, Kokkinou
George, Koutsodontis
Polixeni, Stamatiou
Christoforos, Giatzakis
Anastasios, Anastasakis
Minas, Aslanides Ioannis
Stavrenia, Koukoula
Theoni, Panagiotoglou
Ioannis, Datseris
Miltiadis, Tsilimbaris K.
author_sort Smaragda, Kamakari
collection PubMed
description AIM: To evaluate the frequency and pattern of disease-associated mutations of ABCA4 gene among Greek patients with presumed Stargardt disease (STGD1). MATERIALS AND METHODS: A total of 59 patients were analyzed for ABCA4 mutations using the ABCR400 microarray and PCR-based sequencing of all coding exons and flanking intronic regions. MLPA analysis as well as sequencing of two regions in introns 30 and 36 reported earlier to harbor deep intronic disease-associated variants was used in 4 selected cases. RESULTS: An overall detection rate of at least one mutant allele was achieved in 52 of the 59 patients (88.1%). Direct sequencing improved significantly the complete characterization rate, that is, identification of two mutations compared to the microarray analysis (93.1% versus 50%). In total, 40 distinct potentially disease-causing variants of the ABCA4 gene were detected, including six previously unreported potentially pathogenic variants. Among the disease-causing variants, in this cohort, the most frequent was c.5714+5G>A representing 16.1%, while p.Gly1961Glu and p.Leu541Pro represented 15.2% and 8.5%, respectively. CONCLUSIONS: By using a combination of methods, we completely molecularly diagnosed 48 of the 59 patients studied. In addition, we identified six previously unreported, potentially pathogenic ABCA4 mutations.
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spelling pubmed-59524322018-05-31 Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles Smaragda, Kamakari Vassiliki, Kokkinou George, Koutsodontis Polixeni, Stamatiou Christoforos, Giatzakis Anastasios, Anastasakis Minas, Aslanides Ioannis Stavrenia, Koukoula Theoni, Panagiotoglou Ioannis, Datseris Miltiadis, Tsilimbaris K. J Ophthalmol Research Article AIM: To evaluate the frequency and pattern of disease-associated mutations of ABCA4 gene among Greek patients with presumed Stargardt disease (STGD1). MATERIALS AND METHODS: A total of 59 patients were analyzed for ABCA4 mutations using the ABCR400 microarray and PCR-based sequencing of all coding exons and flanking intronic regions. MLPA analysis as well as sequencing of two regions in introns 30 and 36 reported earlier to harbor deep intronic disease-associated variants was used in 4 selected cases. RESULTS: An overall detection rate of at least one mutant allele was achieved in 52 of the 59 patients (88.1%). Direct sequencing improved significantly the complete characterization rate, that is, identification of two mutations compared to the microarray analysis (93.1% versus 50%). In total, 40 distinct potentially disease-causing variants of the ABCA4 gene were detected, including six previously unreported potentially pathogenic variants. Among the disease-causing variants, in this cohort, the most frequent was c.5714+5G>A representing 16.1%, while p.Gly1961Glu and p.Leu541Pro represented 15.2% and 8.5%, respectively. CONCLUSIONS: By using a combination of methods, we completely molecularly diagnosed 48 of the 59 patients studied. In addition, we identified six previously unreported, potentially pathogenic ABCA4 mutations. Hindawi 2018-04-30 /pmc/articles/PMC5952432/ /pubmed/29854428 http://dx.doi.org/10.1155/2018/5706142 Text en Copyright © 2018 Kamakari Smaragda et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Smaragda, Kamakari
Vassiliki, Kokkinou
George, Koutsodontis
Polixeni, Stamatiou
Christoforos, Giatzakis
Anastasios, Anastasakis
Minas, Aslanides Ioannis
Stavrenia, Koukoula
Theoni, Panagiotoglou
Ioannis, Datseris
Miltiadis, Tsilimbaris K.
Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles
title Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles
title_full Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles
title_fullStr Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles
title_full_unstemmed Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles
title_short Mutation Spectrum of the ABCA4 Gene in a Greek Cohort with Stargardt Disease: Identification of Novel Mutations and Evidence of Three Prevalent Mutated Alleles
title_sort mutation spectrum of the abca4 gene in a greek cohort with stargardt disease: identification of novel mutations and evidence of three prevalent mutated alleles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952432/
https://www.ncbi.nlm.nih.gov/pubmed/29854428
http://dx.doi.org/10.1155/2018/5706142
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