April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Microarray-Based Mutation Analysis of the ABCA4 Gene in Greek Patients With Stargardt Disease: Evidence of Three Prevalent Mutated Alleles
Author Affiliations & Notes
  • S. Kamakari
    School of Medicine, University of Athens, Athens, Greece
    Biogenomica Center For Genetic Research and Analysis, Athens, Greece
  • P. Stamatiou
    Biogenomica Center For Genetic Research and Analysis, Athens, Greece
  • T. Panagiotoglou
    Department of Ophthalmology, School of Medicine University of Crete, Iraklion, Greece
  • C. Tsika
    Department of Ophthalmology, School of Medicine University of Crete, Iraklion, Greece
  • M. Tsilimbaris
    Department of Ophthalmology, School of Medicine University of Crete, Iraklion, Greece
  • Footnotes
    Commercial Relationships  S. Kamakari, None; P. Stamatiou, None; T. Panagiotoglou, None; C. Tsika, None; M. Tsilimbaris, None.
  • Footnotes
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Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4118. doi:
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      S. Kamakari, P. Stamatiou, T. Panagiotoglou, C. Tsika, M. Tsilimbaris; Microarray-Based Mutation Analysis of the ABCA4 Gene in Greek Patients With Stargardt Disease: Evidence of Three Prevalent Mutated Alleles. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4118.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Stargardt (STGD) disease, characterized by central vision impairment, has a juvenile to young adult onset and is the most common form of autosomal recessive macular degeneration. The disease is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette transporter (ABCA4). STGD patients in the Greek population have not been previously genetically characterized for sequence variations in the ABCA4 gene.

Methods: : To evaluate the mutation spectrum in STGD patients from Greece, 19 unrelated patients were analyzed using the ABCR400 microarray and results were confirmed by direct sequencing.

Results: : Two potential mutant alleles were found in 6/19 cases (31.6%), whereas in 6/19 cases (31.6%) only one allele could be identified leading to an overall mutation detection rate of 63.2%. We identified a major disease-associated allele, G1961E, which accounted for 27.8% (5/18) of the mutated alleles. Other frequent ABCA4 alleles in the Greek STGD population included the IVS40+5 G>A splice site variant (16.7% of the detected mutated alleles), the complex allele L541P/A1038V (16.7%), whereas L541P alone or as a complex allele with A1038V was identified with a total detection rate of 22.2%. Based on the mutation spectrum among Greek STGD patients, resulting from the ABCR400 microarray screening, two unrelated patients were subjected to selective screening of the most frequently mutated exons 12,/21, 40 and 42 ofthe ABCA4 gene. Mutations were identified in both patients and involved the complex allele L541P/A1038V in one patient in heterozygous state and the L541P allele and the IVS40+5 G>A splice site variant both in heterozygous state in the second patient. The latter data indicates that an initial cost-effective selective exon pre-screening of all Greek STGD patients can be incorporated in our mutational analysis.

Conclusions: : This is the first systematic study to assess the mutation spectrum of the ABCA4 gene underlying STGD disease in Greece. We identified three prevalent disease-associated alleles, G1961E, L541P alone or as a complex L541P/A1038V allele and the IVS40+5 G>A which accounted for 27.8 %, 22.2% and 16.7% of the mutated alleles, respectively. The overall detection rate by microarray analysis and selective sequencing of the ABCA4 gene was 66.7%. Further studies will help in the definition of the genotype-phenotype relationship in ABCA4-associated retinal dystrophies among Greek patients.

Keywords: retinal degenerations: hereditary • gene screening • mutations 
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