Purpose: To evaluate two families ascertained only for the presence of glaucoma in which both nail-patella syndrome and glaucoma occur in several generations and to determine whether the two diseases are genetically related.
Methods: Ophthalmologic examinations and orthopedic examinations were performed. DNA samples from family members were screened with a microsatellite repeat marker at the argininosuccinate synthetase (ASS) locus at 9q34, and linkage analysis was performed.
Results: Six patients with open-angle glaucoma were found among 13 patients with nail-patella syndrome in family UM:47. Seven patients with glaucoma were found among 11 patients with nail-patella syndrome in family UM:65. In both families, all individuals with glaucoma also had nail-patella syndrome. Two-point linkage analysis resulted in a lod score of 2.98 at a recombination fraction of 0.00 for open-angle glaucoma and nail-patella syndrome.
Conclusions: Linkage results presented here provide strong evidence that the orthopedic and nail anomalies in these two families result from the same nail-patella syndrome locus that has been previously linked to markers at 9q34. These data provide indirect evidence for a possible glaucoma locus at 9q34 and do not allow us to distinguish whether the glaucoma is the result of the nail-patella syndrome mutation or whether there is a separate locus responsible for glaucoma in these families. These studies suggest a need for ophthalmologic examination of individuals with nail-patella syndrome.