Abstract
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. A 10 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 T1GR/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.
Highlights
Glaucoma is a clinically and genetically heterogeneous group of chronic eye diseases characterized by degeneration of the optic nerve head, a distinctive pattern of visual field loss, and a painless progression, usually associated with elevated intraocular pressure (Shields et al 1996)
It is the second most frequent cause of irreversible blindness in the age group of 40 years or older (Quigley 1996), and remarkably, Rodríguez et al (2002) estimated that glaucoma was the main cause of bilateral blindness in a group of “Hispanics”, aged 40 years and older, residing in USA
More than 100 potentially disease causing mutations have been identified in the trabecular meshwork inducible glucocorticoid response” (TIGR)/MYOC gene and remarkably, most of them located in exon 3 (Human Gene Mutation Database Cardiff, HGMD), several large studies have shown that only 3 to 5% from Primary open angle glaucoma (POAG) patients carry mutations in the MYOC (GLC1A) gene (MichelsRautenstrauss et al 1998, Fingert et al 1999, Kubota et al 2000, Michels-Rautenstrauss et al 2002)
Summary
Epidemiological data for glaucoma are vague. Several authors have reported prevalence rates which are impossible to compare because of differences in diagnostic criteria, in the ages of onset and the ethnic affiliation of the subjects studied. Quigley et al (2001) estimated the prevalence of glaucoma in 4774 Hispanic subjects living in USA. They found an intermediate value (1.97%) between those reported for Caucasians and Afro-Americans. Besides the many sporadic cases, inheritance of the disease, especially the COAGs shows great variation (Wiggs et al 2000). In some families it conforms to Mendelian segregation ratios whereas in others it presents complex patterns, i.e., they only show aggregation of patients. Among the families with Mendelian inheritance, different modes of inheritance have been documented, but in most cases with COAG and JOAG the segregation is autosomal dominant, while PCG follows a recessive pattern of inheritance (Sarfarazi 1997)
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