Genetic linkage of autosomal dominant primary open angle glaucoma to chromosome 3q in a Greek pedigree

A locus for juvenile onset open angle glaucoma (OAG) has been assigned to c hromosome Iq in families with autosomal dominant inheritance (GLC1A), due t o mutations in the TIGR/MYOC gene. For adult onset OAG, called primary open angle glaucoma or POAG, five loci have so far been mapped to different chr omosomes (GLC1B-GLC1F). Except for the GLC1B locus, the other POAG loci hav e so far been reported only in single large pedigrees. We studied a large f amily identified in Epirus, Greece, segregating POAG in an autosomal domina nt fashion. Clinical findings included increased cup to disc ratio (mean 0. 7), characteristic glaucomatous changes in the visual field, and intraocula r pressure before treatment more than 21 mmHg (mean 31 mmHg), with age at d iagnosis 33 years and older. Linkage analysis was performed between the dis ease phenotype and microsatellite DNA polymorphisms. Linkage was establishe d with a group of DNA markers located on chromosome 3q, where the GLC1C loc us has previously been described in one large Oregon pedigree. A maximal mu ltipoint lod score of 3.88 was obtained at marker D351763 (penetrance 80%). This represents the second POAG family linked to the GLC1C locus on chromo some 3q, and haplotype analysis in the two families suggests an independent origin of the genetic defect.