Autosomal dominant Stargardt-like macular dystrophy: founder effect and reassessment of genetic heterogeneity

Arch Ophthalmol. 2001 Apr;119(4):564-70. doi: 10.1001/archopht.119.4.564.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 6 / genetics
  • DNA / analysis
  • Female
  • Founder Effect*
  • Genealogy and Heraldry
  • Genes, Dominant*
  • Genetic Heterogeneity*
  • Genetic Linkage / genetics
  • Genetic Markers
  • Haplotypes
  • Humans
  • Macular Degeneration / genetics*
  • Male
  • Pedigree


  • Genetic Markers
  • DNA