A NOVEL MUTATION IN THE GLC1A GENE CAUSES JUVENILE OPEN-ANGLE GLAUCOMA IN 4 FAMILIES FROM THE ITALIAN REGION OF PUGLIA

Background: Primary open-angle glaucoma encompasses a complex of poten tially blinding ocular diseases characterized by a normal-appearing an gle of the anterior chamber, a characteristic degeneration of the opti c nerve with resultant typical visual field defects, and usually, an e levated intraocular pressure. It can be subdivided into 2 groups accor ding to the age at onset: the more prevalent chronic open-angle glauco ma diagnosed after 40 years of age, and the less common juvenile form, which occurs between 3 years of age and early adulthood. A locus for primary open-angle glaucoma (GLC1A) has been mapped to a 3-centimorgan region of the long arm of chromosome 1 ( 1q23-25). Recently, the myoc ilin (MYOC) gene, located in this chromosomal interval, has been found mutated in several patients affected by primary open-angle glaucoma. Objective: To describe the clinical and molecular genetic features of 4 pedigrees affected by autosomal dominant juvenile open-angle glaucom a, all from the Italian region of Puglia. Methods: Clinical study, gon ioscopy, automated perimetry, and DNA analysis were performed on sever al members of the 4 families. Results: We identified a new molecular d efect (1177GACA-->T) in the third exon of the GLC1A gene. This mutatio n is present in all affected persons and in 2 still phenotypically nor mal persons. Conclusion: Our results are important for diagnostic purp oses because it is now possible to identify asymptomatic carriers, for whom clinical surveillance for the early detection and treatment of g laucoma may be suggested.