title: Genomic screening of ABCA4 and array CGH analysis underline the genetic variability of Greek patients with inherited retinal diseases.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Tsipi
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Tzetis
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Kosma
authors.affiliation: 1st Department of Ophthalmology, G. Gennimatas Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Marilita
authors.initials: M
authors.lastname: Moschos
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Research Institute for the Study of Genetic and Malignant Disorders in Childhood, St. Sophias Children's Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Braoudaki
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Myrto
authors.initials: M
authors.lastname: Poulou
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Research Institute for the Study of Genetic and Malignant Disorders in Childhood, St. Sophias Children's Hospital, Athens, Greece.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
authors.affiliation: Department of Medical Genetics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Kitsiou-Tzeli
keywords: ABCA4 mutations; Stargardt's disease; autosomal recessive cone-rod dystrophy; autosomal recessive retinitis pigmentosa