Complex inheritance of ABCR mutations in Stargardt disease: linkage disequilibrium, complex alleles, and pseudodominance.
Stargardt disease is a recessively transmitted disease caused by mutations in the ABCR gene. Linkage disequilibrium has recently been reported between a polymorphism, 2828 A, and a common Western European founder mutation, 2588 C. Here, we confirm this linkage disequilibrium in a North American population. We also describe two complex alleles involving the 2828 A and 2588 C alterations and suggest a possible order of clinical severity of mutations identified in trans to the complex alleles. Finally, we report pseudodominance of Stargardt disease in a family with the 2588 C mutation, further supporting a high frequency of carriers for ABCR mutations in our population.
Shroyer
N F
NF
Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Lewis
R A
RA
Lupski
J R
JR
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D012374:Rod Cell Outer Segment / Q000378:metabolism
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters