Are microarrays useful in the screening of ABCA4 mutations in Italian patients affected by macular degenerations?

Abstract : Recessive Stargardt disease is due to mutations in the retina-specific ABC transporter gene. Established strategies for molecular characterization of this gene include direct detection by a microarray interrogating approximately 500 DNA variations and a scanning denaturing HPLC methodology. : Because 11 mutations were reported to account for approximately 50% of molecular defects in the Italian population, we evaluated an alternative open microchip-based assay for a fast and simplified level 1 screening for these mutations. : This approach allowed the characterization of both mutated alleles in 4% and one mutated allele in 43% of cases when applied to a cohort of 47 Stargardt patients. In the same patients, further investigation by denaturing HPLC for complete characterization identified both mutated alleles in 51% and one mutated allele in 19% of cases, allowing the detection of 38 different mutations, five of which had never been described. Notably, new mutations account for a high proportion (13%) of molecular defects in our patient cohort. : This finding raises the question about the choice of the optimal diagnostic strategy for complete genotyping of the Clin Chem Lab Med 2008;46:1250–5.