Microarray-based mutation analysis of the ABCA4 gene inSpanish patients with Stargardt disease: evidence of a prevalent mutatedallele

摘要

Purpose: To evaluate, in a pool of affected families, the mutationspectrum in Stargardt patients from Spain, using the ABCR400 microarraythat contains described sequence variants in the gene encoding for thephotoreceptor specific ATP-binding cassette transporter (ABCA4).Methods: We analyzed 76 Spanish patients with STGD1 for apopulation-specific survey on the sequence variations in the ABCA4gene, using the ABCR400 microarray.Results: Potential disease-associated alleles were identified in 91of the 152 STGD1 chromosomes studied, resulting in a detection rate of60%. The two mutant alleles were found in 33/76 patients (43%), whereasin 25/76 cases (33%) only one allele could be identified. In theremaining 18 patients no mutations were found. In total, we identified40 sequence variations that could be related to the disease. The vastmajority of these substitutions (35/40) were missense mutations. Threeframeshift mutations and two splicing variants were also found.Conclusions: We identified a major disease-associated allele,R1129L, which accounted for 24% of the mutated alleles detected, and ahigh frequency (12%) of complex alleles.