title: Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.
abstract: The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.
authors.affiliation: Department of Human Genetics, University Medical Centre-Nijmegen, 6500 HB Nijmegen, The Netherlands. A.Maugeri@antrg.azn.nl
authors.forename: A
authors.initials: A
authors.lastname: Maugeri
authors.forename: B J
authors.initials: BJ
authors.lastname: Klevering
authors.forename: K
authors.initials: K
authors.lastname: Rohrschneider
authors.forename: A
authors.initials: A
authors.lastname: Blankenagel
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: A F
authors.initials: AF
authors.lastname: Deutman
authors.forename: C B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: F P
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D005808:Genes, Recessive / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009426:Netherlands; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters