GENETIC-HETEROGENEITY OF PRIMARY OPEN-ANGLE GLAUCOMA AND OCULAR HYPERTENSION - LINKAGE TO GLC1A ASSOCIATED WITH AN INCREASED RISK OF SEVEREGLAUCOMATOUS OPTIC NEUROPATHY

The GLC1A locus for autosomal dominant juvenile and middle age onset p rimary open angle glaucoma (GAG) has been mapped to chromosome 1q21-q3 1. GAG, however, is a heterogeneous disease. We tested linkage of OAG and ocular hypertension (OHT); a major risk factor for GAG, to GLC1A i n eight French families with multiple cases of juvenile and middle age onset GAG. There was strong evidence of genetic heterogeneity, four f amilies being Linked to GLC1A and two or three others being unlinked, depending on whether the complete OAG phenotype was analysed alone or jointly with OHT. Peak intraocular pressure (IOP) did not differ signi ficantly between the two groups of families, while linkage to GLC1A co nferred a highly increased risk of developing OAG and of having severe glaucomatous optic neuropathy. Testing linkage of familial OAG to GLC 1A may therefore have prognostic value too.