Objectives: To characterize a disease-associated haplotype in 7 families wi
th autosomal dominant Stargardt-like macular dystrophy and to determine whe
ther these families share a common ancestor.
Methods: Twenty-five polymorphic DNA markers spanning known dominant Starga
rdt-like gene loci were used to determine the haplotype associated with dis
ease. 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. Th
e same DNA haplotype on chromosome 6q16 was shared by all evaluated affecte
d members within the 7 families. In addition, we were able to genealogicall
y 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 th
e critical region for the gene to approximately 1000 kilobases (kb) and eli
minated part or all of 9 candidate disease-causing genes.
Conclusions: Our study indicates that most reported cases of autosomal domi
nant 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 individu
als with phenotypically similar retinal conditions.
Clinical Relevance: The disease-associated haplotype allows for more accura
te genetic counseling to be given to individuals with a Stargardt-like phen
otype inherited in an autosomal dominant pattern.