Clinical and genetic heterogeneity of autosomal dominant open angle glaucoma (adOAG) in Italy

Purpose: To identify adOAG locus/i by linkage analysis. Methods: We have identified several ad juvenile and adult POAG families and have analysed their clinical phenotypes and mapped the adOAG Iocus/i by linkage analysis. Families were recruited through a multicentric effort and the diagnoses were confirmed by ophtalmological examination. We selected 40 POAG families with several patients in at least 3 generations. DNA was obtained from affected and non affected members of these families. Linkage analysis was carried out using several markers mapped at Chr 1 q23-25 closely linked to the already mapped GLC1A locus. Results: We identified some JOAG families linked and others not linked to the GLC1A locus. No association to this locus was seen in adult adOAG families. Moreover we have identified 4 unrelated families from a small southern Italian village. In these families we found both the adult and the juvenile forms of POAG. Linkage analysis showed association with GLC1A locus and all the affected members carry a common haplotype (strong indication of a "founder effect"). Comparison of the allele shared by the GLC1A haplotype in affected e non affected members of this families allowed the identification of key ricombinants narrowing the GLC1A critical region between D1S452 and D1S242. Conclusions: We confirmed the genetic heterogeneity of POAG and in some families associated with the GLC1A locus we also observed clinical heterogeneity. A more precise correlation between genotype and phenotype will be instrumental in the identification of all the factors involved in this disorder.