Juvenile glaucoma linked to GLCIA in a Panamanian family

Purpose: To carry out clinical and genetic characterization of juvenile- onset primary open-angle glaucoma (POAG) inherited as an autosomal dominant trait in a Panamanian family. Methods: Twenty-two members of a six-generation Panamanian family underwent an ophthalmologic evaluation. Blood samples were collected from 20 of these individuals for preparation of DNA for use in screening of microsatellite repeat genetic markers via polymerase chain reaction. Results: Eleven living family members convering 4 generations were diagnosed as affected with open-angle glaucoma of primary juvenile onset. Four of 3 other at-risk individuals examined and enrolled were characterized as unaffected and two as indeterminate. Two additional individuals were not included in this study because they were too young to characterize or to provide a blood sample. Three spouses of affected family members were also examined and found not to have glaucoma. Of clinical importance was the finding of markedly elevated intraocular pressure (IOP) in 2 affected brothers, both of whom were advised to have urgent filtration surgery; the finding of elevated IOP in the only seeing eye of the mother of these brothers, causing us to advise her to pursue more aggressive treatment; and the finding of early signs of glaucoma in a previously undiagnosed 9-year- old family member. Linkage analysis using selected microsatellite repeat markers in the 1q21-q31 region revealed strong evidence for linkage to the GLCIA gene with a maximum load score 3.75 for marker D1S431 at a recombination fraction of 0.00. Conclusions: The most likely interpretation of our data is that a mutation in the GLCIA gene is responsible for juvenile- onset POAG in this Panamanian family, thus expanding the countries of origin where this gene has been found to exist. The members of families with GLCIA glaucoma now reported from only a few centers worldwide raise questions about whether this disease may be more common than once thought. Evaluation of treatment histories and clinical outcomes in members of this and other previously reported families indicates that ophthalmologists need to understand the necessity for urgent filtration surgery in most cases of GLCIA glaucoma if vision is to be preserved.