title: Spectrum of the ABCA4 gene mutations implicated in severe retinopathies in Spanish patients.
abstract: OBJECTIVE
  The purpose of this study is to describe the spectrum of mutations in the ABCA4 gene found in Spanish patients affected with several retinal dystrophies.
  
  
  METHODS
  Sixty Spanish families with different retinal dystrophies were studied. Samples were analyzed for variants in all 50 exons of the ABCA4 gene by screening with the ABCR400 microarray, and results were confirmed by direct sequencing. Haplotype analyses were also performed. For those families with only one mutation detected by the microarray, denaturing (d)HPLC was performed to complete the mutational screening of the ABCA4 gene.
  
  
  RESULTS
  The sequence analysis of the ABCA4 gene led to the identification of 33 (27.5%) potential disease-associated alleles among the 60 patients. These comprised 16 distinct sequence variants in 25 of the 60 subjects investigated. For autosomal recessive cone-rod dystrophy (arCRD), we found that 50% of the CRD families with the mutation had two recurrent changes (2888delG and R943Q). For retinitis pigmentosa (RP) and autosomal dominant macular dystrophy (adMD), one putative disease-associated allele was identified in 9 of the 27 and 3 of the 7 families, respectively.
  
  
  CONCLUSIONS
  In the population studied, ABCA4 plays an important role in the pathogenesis of arCRD. However, mutations in this gene are less frequently identified in other retinal dystrophies, like RP or adMD, and therefore it is still not clear whether ABCA4 is involved as a modifying factor or the relationship is a fortuitous association.
authors.affiliation: Facultad de Biología, Universidad de Vigo,Vigo, Spain. dianaval@univigo.es
authors.forename: Diana
authors.initials: D
authors.lastname: Valverde
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.forename: Jana
authors.initials: J
authors.lastname: Aguirre-Lamban
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Miguel
authors.initials: M
authors.lastname: Carballo
authors.forename: Guillermo
authors.initials: G
authors.lastname: Antiñolo
authors.forename: José Maria
authors.initials: JM
authors.lastname: Millán
authors.forename: Blanca
authors.initials: B
authors.lastname: Garcia Sandoval
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000483:Alleles; D002851:Chromatography, High Pressure Liquid; D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters