Autosomal dominant Stargardt-like macular dystrophy: founder effect and reassessment of genetic heterogeneity.
Arch Ophthalmol
; 119(4): 564-70, 2001 Apr.
Article
in En
| MEDLINE
| ID: mdl-11296022
ABSTRACT
OBJECTIVES:
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. CLINICAL RELEVANCE 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Heterogeneity
/
Founder Effect
/
Genes, Dominant
/
Macular Degeneration
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Arch Ophthalmol
Year:
2001
Document type:
Article