Microarray-based mutation analysis of the ABCA4 gene in Spanish patients with Stargardt disease: evidence of a prevalent mutated allele.
OBJECTIVE
To evaluate, in a pool of affected families, the mutation spectrum in Stargardt patients from Spain, using the ABCR400 microarray that contains described sequence variants in the gene encoding for the photoreceptor specific ATP-binding cassette transporter (ABCA4).


METHODS
We analyzed 76 Spanish patients with STGD1 for a population-specific survey on the sequence variations in the ABCA4 gene, using the ABCR400 microarray.


RESULTS
Potential disease-associated alleles were identified in 91 of the 152 STGD1 chromosomes studied, resulting in a detection rate of 60%. The two mutant alleles were found in 33/76 patients (43%), whereas in 25/76 cases (33%) only one allele could be identified. In the remaining 18 patients no mutations were found. In total, we identified 40 sequence variations that could be related to the disease. The vast majority of these substitutions (35/40) were missense mutations. Three frameshift 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 a high frequency (12%) of complex alleles.
Valverde
Diana
D
Departmento de Bioquímica, Genética e Inmunología, Facultad de Biología, Universidad de Vigo, Vigo, Spain. dianaval@uvigo.es
Riveiro-Alvarez
Rosa
R
Bernal
Sara
S
Jaakson
Kaie
K
Baiget
Montserrat
M
Navarro
Rafael
R
Ayuso
Carmen
C
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D001120:Arginine; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D014644:Genetic Variation; D006801:Humans; D007930:Leucine; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D013030:Spain
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D004274:DNA, Recombinant; D001120:Arginine; D007930:Leucine