title: Frequency of ABCA4 mutations in 278 Spanish controls: an insight into the prevalence of autosomal recessive Stargardt disease.
abstract: 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.
authors.affiliation: Fundación Jimenez Diaz, Genetics Department, Madrid, Spain. rriveiro@fjd.es
authors.forename: R
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: J
authors.initials: J
authors.lastname: Aguirre-Lamban
authors.forename: M Angel
authors.initials: MA
authors.lastname: Lopez-Martinez
authors.forename: M Jose
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
authors.forename: D
authors.initials: D
authors.lastname: Cantalapiedra
authors.forename: E
authors.initials: E
authors.lastname: Vallespin
authors.forename: A
authors.initials: A
authors.lastname: Avila-Fernandez
authors.forename: C
authors.initials: C
authors.lastname: Ramos
authors.forename: C
authors.initials: C
authors.lastname: Ayuso
mesh_terms: 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
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters