TY - JOUR
TI - Genomic screening of ABCA4 and array CGH analysis underline the genetic variability of Greek patients with inherited retinal diseases
AU - Tsipi, M.
AU - Tzetis, M.
AU - Kosma, K.
AU - Moschos, M.
AU - Braoudaki, M.
AU - Poulou, M.
AU - Kanavakis, E.
AU - Kitsiou-Tzeli, S.
JO - Meta Gene
PY - 2016
VL - 8
TODO - null
SP - 37-43
PB - Elsevier B.V.
SN - 2214-5400
TODO - 10.1016/j.mgene.2016.02.002
TODO - ABCA4 gene;  adult;  Article;  child;  choroid capillary layer;  clinical article;  color vision defect;  comparative genomic hybridization;  computer model;  controlled study;  copy number variation;  dark adaptation;  DNA flanking region;  DNA hybridization;  electroretinography;  female;  fluorescence angiography;  gene;  gene amplification;  gene deletion;  gene sequence;  genetic screening;  genetic variability;  Greek (people);  human;  male;  missense mutation;  mutational analysis;  nonsense mutation;  optical coherence tomography;  polymerase chain reaction;  priority journal;  retinitis pigmentosa;  retinopathy;  RNA splicing;  school child;  segregation analysis;  single nucleotide polymorphism;  Stargardt disease;  visual acuity
TODO - Background: Retinal dystrophies are a clinically and genetically heterogeneous group of disorders which affect more than two million people worldwide. The present study focused on the role of the ABCA4 gene in the pathogenesis of hereditary retinal dystrophies (autosomal recessive Stargardt disease, autosomal recessive cone-rod dystrophy, and autosomal recessive retinitis pigmentosa) in patients of Greek origin. Materials and methods: Our cohort included 26 unrelated patients and their first degree healthy relatives. The ABCA4 mutation screening involved Sanger sequencing of all exons and flanking regions. Evaluation of novel variants included sequencing of control samples, family segregation analysis and characterization by in silico prediction tools. Twenty five patients were also screened for copy number variations by array-comparative genomic hybridization. Results: Excluding known disease-causing mutations and polymorphisms, two novel variants were identified in coding and non-coding regions of ABCA4. Array-CGH analysis revealed two partial deletions of USH2A and MYO3A in two patients with nonsyndromic autosomal recessive retinitis pigmentosa. Conclusions: The ABCA4 mutation spectrum in Greek patients differs from other populations. Bioinformatic tools, segregation analysis along with clinical data from the patients seemed to be crucial for the evaluation of genetic variants and particularly for the discrimination between causative and non-causative variants. © 2016 The Authors.
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