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 potentially blinding ocular diseases characterized by a normal-appearing angle of the anterior chamber, a characteristic degeneration of the optic nerve with resultant typical visual field defects, and usually, an elevated intraocular pressure. It can be subdivided into 2 groups according to the age at onset: the more prevalent chronic open-angle glaucoma 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 myocilin (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 glaucoma, all from the Italian region of Puglia. Methods: Clinical study, gonioscopy, automated perimetry, and DNA analysis were performed on several members of the 4 families. Results: We identified a new molecular defect (1177GACA-->T) in the third exon of the GLC1A gene. This mutation is present in all affected persons and in 2 still phenotypically normal persons. Conclusion: Our results are important for diagnostic purposes because it is now possible to identify asymptomatic carriers, for whom clinical surveillance for the early detection and treatment of glaucoma may be suggested.