Genomic screening of ABCA4 and array CGH analysis underline the genetic variability of Greek patients with inherited retinal diseases

• Sixteen known pathological genetic variants were identified in ABCA4 gene in Greek patients with retinal dystrophies.
• Two novel variants were found in patients with Stargardt’s disease and cone-rod dystrophy respectively.
• Two reported mutations in Stargardt's patients were identified in retinitis pigmentosa and cone-rod dystrophy patients.
• The mutations p.Gly1961Glu and p.Ala1038Val, which are common in other populations, where also found in our cohort consisted of 26 Greek patients.
• Array-comparative genome hybridization revealed large deletions in two out of the 25 cases studied.

BackgroundRetinal 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 methodsOur 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.ResultsExcluding 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.ConclusionsThe 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.