GENETIC-MAPPING OF AUTOSOMAL-DOMINANT PRIMARY OPEN-ANGLE GLAUCOMA (POAG) IN SARDINIA

Primary open-angle glaucoma (POAG) can be subdivided into two groups a ccording to age of onset: (1) the more prevalent middle to late-age-on set chronic open-angle glaucoma (COAG) diagnosed after age 40, and (2) the less common form, juvenile open-angle glaucoma (JOAG), which occu rs between 3 years of age and early adulthood. Susceptibility to eithe r COAG or JOAG has been found to be inherited. The discovery of severa l genetic markers spanning the region 1q21-q24 in genetic linkage with autosomal dominant juvenile open-angle glaucoma (adJOAG) represents a major breakthrough towards the localisation of gene(s) responsible fo r the disease. Linkage analysis is a powerful means of distinguishing disease loci in large families with dominant disease. However the size of the group of families may represent a crucial factor for the linka ge analysis. Sardinia is an island with a relatively isolated ethnic g roup showing a relatively high frequency of ad JOAG and COAG (Fossarel lo et al., 1994) and it is genetically more homogeneous than most West ern populations. Therefore it represents an ideal ethnic group to sear ch for linkage. We identified 18 families affected by POAG in which th e disease appears to be inherited as autosomic dominant trait. In all families but two, occurrence of both JOAG and COAG in the same kindred was observed. Identification of adPOAG locus was performed by linkage analysis using 9 microsatellite markers spanning the region 1q21-q24. No significant linkage was observed. Our findings provide further evi dence for genetic heterogeneity in autosomal dominant primary open ang le glaucoma, even in a geographic area where a relatively homogeneous genetic background exists.