An analysis of ABCR mutations in British patients with recessive retinal dystrophies.
OBJECTIVE
Several reports have shown that mutations in the ABCR gene can lead to Stargardt disease (STGD)/fundus flavimaculatus (FFM), autosomal recessive retinitis pigmentosa (arRP), and autosomal recessive cone-rod dystrophy (arCRD). To assess the involvement of ABCR in these retinal dystrophies, the gene was screened in a panel of 70 patients of British origin.


METHODS
Fifty-six patients exhibiting the STGD/FFM phenotype, 6 with arRP, and 8 with arCRD, were screened for mutations in the 50 exons of the ABCR gene by heteroduplex analysis and direct sequencing. Microsatellite marker haplotyping was used to determine ancestry.


RESULTS
In the 70 patients analyzed, 31 sequence changes were identified, of which 20 were considered to be novel mutations, in a variety of phenotypes. An identical haplotype was associated with the same pair of in-cis alterations in 5 seemingly unrelated patients and their affected siblings with STGD/FFM. Four of the aforementioned patients were found to carry three alterations in the coding sequence of the ABCR gene, with two of them being in-cis.


CONCLUSIONS
These results suggest that ABCR is a relatively polymorphic gene. Because putative mutations have been identified thus far only in 25 of 70 patients, of whom only 8 are compound heterozygotes, a large number of mutations have yet to be ascertained. The disease haplotype seen in the 5 patients carrying the same "complex" allele is consistent with the presence of a common ancestor.
Papaioannou
M
M
Department of Molecular Genetics, Institute of Ophthalmology, London, UK.
Ocaka
L
L
Bessant
D
D
Lois
N
N
Bird
A
A
Payne
A
A
Bhattacharya
S
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D004247:DNA / Q000032:analysis; D004596:Electroretinography; D006239:Haplotypes; D020180:Heteroduplex Analysis; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D012374:Rod Cell Outer Segment / Q000473:pathology*; D017422:Sequence Analysis, DNA; D006113:United Kingdom
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D004247:DNA