Autosomal dominant Stargardt-like macular dystrophy: founder effect and reassessment of genetic heterogeneity.
OBJECTIVE
To characterize a disease-associated haplotype in 7 families with autosomal dominant Stargardt-like macular dystrophy and to determine whether these families share a common ancestor.


METHODS
Twenty-five polymorphic DNA markers spanning known dominant Stargardt-like gene loci were used to determine the haplotype associated with disease. In addition, an extensive genealogical investigation searching for a common ancestor shared by all of the 7 families was performed.


RESULTS
We clinically evaluated 171 patients and genotyped 145 samples. The same DNA haplotype on chromosome 6q16 was shared by all evaluated affected members within the 7 families. In addition, we were able to genealogically join all of the families into one larger family consisting of 31 branches and 2314 individuals. Twenty-seven branches have known living descendants, with 7 branches having affected family members. In addition, we refined the critical region for the gene to approximately 1000 kilobases (kb) and eliminated part or all of 9 candidate disease-causing genes.


CONCLUSIONS
Our study indicates that most reported cases of autosomal dominant Stargardt-like macular dystrophy in North America are part of a single larger family associated with a gene locus on chromosome 6q16. Furthermore, the DNA haplotype associated with disease is useful in excluding individuals with phenotypically similar retinal conditions.


CONCLUSIONS
The disease-associated haplotype allows for more accurate genetic counseling to be given to individuals with a Stargardt-like phenotype inherited in an autosomal dominant pattern.
Donoso
L A
LA
Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9057. Albert.Edwards@UTSouthwestern.edu
Frost
A T
AT
Stone
E M
EM
Weleber
R G
RG
MacDonald
I M
IM
Hageman
G S
GS
Cibis
G W
GW
Ritter
R
R
Edwards
A O
AO
D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004247:DNA / Q000032:analysis; D005260:Female; D018703:Founder Effect; D005789:Genealogy and Heraldry; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D010375:Pedigree
D005819:Genetic Markers; D004247:DNA