Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy

Am J Hum Genet. 2000 Oct;67(4):960-6. doi: 10.1086/303079. Epub 2000 Aug 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Alleles
  • Amino Acid Substitution / genetics
  • Base Sequence
  • Genes, Recessive / genetics*
  • Genotype
  • Germany
  • Humans
  • Mutation / genetics*
  • Netherlands
  • Phenotype
  • Polymorphism, Single-Stranded Conformational
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology


  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters