Glaucoma is the second most frequent cause of irreversible blindness worldwide. Genetic factors have
been implicated in the development of the disease. So far six loci (GLC1A-GLC1F) and two genes
(TIGR/MYOC and OPTN) are involved in the development of juvenile (JOAG) and adult onset or chronic primary
open angle glaucoma (COAG), while two loci (GLC3A,GLC3B) and one gene (CYP1B1) are known for
primary congenital glaucoma (PCG). Here we summarize the results of the first genetic studies of glaucoma in
Costa Rica. Nine families: 1 with JOAG, 1 with PCG and 7 with COAG were screened for mutations at the
known genes. A10 bp duplication, 1546-1555dupTCATGCCACC, at the CYP1B1 gene, causes, in homozygous
state, glaucoma in the consanguineous PCG family. This mutation has been found in different countries and generates
an early stop codon that termitates protein synthesis 140 amino acids earlier than the normal allele. In
exon 1 of the TIGR/MYOC the innocuous Arg76Lys variant was found in two of the COAG families. In the
OPTN gene two variants in the coding region (Thr34Thr, Met 98Lys) and 7 intronic changes were found in other
Costa Rican glaucoma patients. One of the COAG families was chosen for a genome scan with 379 microsatellite
markers and linkage analysis. LOD scores “suggestive” of linkage were obtained for several chromosomal
regions. Evidence indicates that hereditary glaucoma in Costa Rica is highly heterogeneous and that further
studies in the country will probably disclose some up to now unknown genes responsible for the disease

Keywords: glaucoma, TIGR/MYOC, OPTN, CYP1B1, genome scan, linkage analysis