Frequency of ABCA4 mutations in 278 Spanish controls: an insight into the prevalence of autosomal recessive Stargardt disease.
OBJECTIVE
To determine the carrier frequency of ABCA4 mutations in order to achieve an insight into the prevalence of autosomal recessive Stargardt disease (arSTGD) in the Spanish population.


METHODS
arSTGD patients (n = 133) were analysed using ABCR400 microarray and sequencing. Control subjects were analysed by two different strategies: 200 individuals were screened for the p.Arg1129Leu mutation by denaturing-HPLC and sequencing; 78 individuals were tested for variants with the microarray and sequencing.


RESULTS
For the first strategy in control subjects, the p.Arg1129Leu variant was found in two heterozygous individuals, which would mean a carrier frequency for any variant of approximately 6.0% and a calculated arSTGD prevalence of 1:1000. For the second strategy, carrier frequency was 6.4% and therefore an estimated prevalence of the disease of 1:870.


CONCLUSIONS
Calculated prevalence of arSTGD based on the ABCA4 carrier frequency could be considerably higher than previous estimation. This discrepancy between observed (genotypic) and estimated (phenotypic) prevalence could be due to the existence of non-pathological or low penetrance alleles, which may result in late-onset arSTGD or may be implicated in age-related macular degeneration. This situation should be regarded with special care when genetic counselling is given and further follow-up of these patients should be recommended.
Riveiro-Alvarez
R
R
Fundación Jimenez Diaz, Genetics Department, Madrid, Spain. rriveiro@fjd.es
Aguirre-Lamban
J
J
Lopez-Martinez
M Angel
MA
Trujillo-Tiebas
M Jose
MJ
Cantalapiedra
D
D
Vallespin
E
E
Avila-Fernandez
A
A
Ramos
C
C
Ayuso
C
C
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005787:Gene Frequency; D005808:Genes, Recessive; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D015995:Prevalence; D013030:Spain / Q000453:epidemiology
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters