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

The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA 4; previously denoted "ABCR") is mutated in most patients with autosomal re cessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In a ddition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dyst rophy (CRD) have been found to have ABCA4 mutations. To evaluate the import ance of the ABCA4 gene as a cause of Abi CRD, we selected 5 patients with A R CRD and 15 patients with isolated CRD, all from Germany and The Netherlan ds. Single-strand conformation-polymorphism analysis and sequencing reveale d 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were d etected in one allele. One complex ABCA4 allele (L541P;A1038V) was found ex clusively in German patients with CRD; one patient carried this complex all ele 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 g ene's involvement in an as-yet-unknown proportion of cases with AR RP, stre ngthens the idea that mutations in the ABCA4 gene could be the most frequen t cause of inherited retinal dystrophy in humans.