Objectives: To demonstrate the inheritance of the pigment dispersion syndrome in 4 families and to determine the location of a gene responsible for this syndrome.
Patients: Fifty-four members of 4 families affected by the pigment dispersion syndrome and pigmentary glaucoma. All 4 families are white. Two of the pedigrees are of Irish descent, and 2 are of mixed western European descent that includes some Irish ancestry.
Interventions: Individuals from 4 pedigrees affected by the pigment dispersion syndrome and their spouses were clinically examined for evidence of the pigment dispersion syndrome. DNA samples from patients and appropriate family members were used for a genome screen using microsatellite repeat markers distributed throughout the human genome. Genotypes were used for linkage analysis to identify markers segregating with the disease trait.
Results: Twenty-eight patients showed clinical evidence of the pigment dispersion syndrome. Of these, 14 also had elevated intraocular pressures requiring medical or surgical treatment or both. Significant linkage was observed between the disease phenotype and markers located on the telomere of the long arm of human chromosome 7 (i.e., 7q35-q36). The maximum 2-point lod score (i.e., Zmax) for a single pedigree (i.e., PDS5) was 5.72 at theta = 0 for markers D7S2546 and D7S550. An analysis of affected recombinant individuals demonstrated that the responsible gene is located in a 10-centimorgan interval between markers D7S2462 and D7S2423.
Conclusions: The pigment dispersion syndrome was found to be inherited as an autosomal dominant trait in 4 affected pedigrees. The gene responsible for the syndrome in these 4 families maps to the telomeric end of the long arm of chromosome 7 (i.e., 7q35-q36). Locating a gene responsible for this condition is the first step toward the isolation of the gene itself. Characterization of the responsible gene will help elucidate the pathophysiology of this disease and potentially will lead to new methods of diagnosis and treatment.