A GENE RESPONSIBLE FOR THE PIGMENT DISPERSION SYNDROME MAPS TO CHROMOSOME 7Q35-Q36

Objectives: To demonstrate the inheritance of the pigment dispersion s yndrome in 4 families and to determine the location of a gene responsi ble for this syndrome. Patients: Fifty-four members of 4 families affe cted 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 ancestr y. Interventions: Individuals from 4 pedigrees affected by the pigment dispersion syndrome and their spouses were clinically examined for ev idence of the pigment dispersion syndrome. DNA samples from patients a nd appropriate family members were used for a genome screen using micr osatellite repeat markers distributed throughout the human genome. Gen otypes 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 el evated intraocular pressures requiring medical or surgical treatment o r both. Significant linkage was observed between the disease phenotype and markers located on the telomere of the long arm of human chromoso me 7 (ie, 7q35-q36). The maximum 2-paint lod score (ie, z(max)) for a single pedigree (ie, 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 betw een markers D7S2462 and D7S2423. Conclusions: The pigment dispersion s yndrome was found to be inherited as an autosomal dominant trait in 4 affected pedigrees. The gene responsible for the syndrome in these 4 f amilies maps to the telomeric end of the long arm of chromosome 7 (ie, 7q35-q36). Locating a gene responsible for this condition is the firs t step toward the isolation of the gene itself. Characterization of th e responsible gene will help elucidate the pathophysiology of this dis ease and potentially will lead to new methods of diagnosis and treatme nt.