Glaucoma in Costa RIca. Initial approaches

Abstract

El glaucoma es la segunda causa de ceguera irreversible en el mundo. El componente genetico de algunos de los distintos tipos ha sido demostrado: seis loci (GLC1AGLC1F) y dos genes (TIGNMY0C y OPTN) se conocen. hasta ahora, como responsables de la aparicion de glauet)-- mas primarios de angulo abierto tanto del tipo juvenil (JOAG) como del tipo de adultos (COAG). Ademas, dos loci (GLC3A,GLC3B) y un gene (CYPIBI) se hen descubierto coma causal del tipu primariu congenito (PCG). Sc presenta una relaciort de los estudios geneticos iniciales sobre el glaucoma en Costa Rica. Nueve families: 1 con JOAG, 1 con PCG y 7 con COAG se estudiaron en bused de mutaciones en los genes conocidos. Una duplicaciOn de 10 ph, 1546-1555dupTCATGCCACC, en el gene CYPIBI, causa glaucoma en condicionhornocigraa cn una fatutliaconsaguinca con PCG. Esta mutation se ha encontrado en otros paises y origins un codon dc terminacion prematuro que codifica una proteins 140 aminoacidos mas cotta que la normal. En dos de las families eon COAG encondo tins variante inocua Arg76Lys en el exon I del gen TIGR/MYOC. Otros pacienies prescntaron. en el gene OPTN, dos variantes en la region codificarne (Thr34Thr. Met 9SLys) y 7 cambios intrOnicos. Una de las familia.; con COAG cumple con los requerimientos minimos parr tut anilisis de ligamicnto, por lo que sc utilizaron 379 marcadores microsateliticos pars mapear el gen causante de Is enfermedad. No sc obtuvieron valores LOD quc elaramente impliearan a alguna region criamosamica. La evidencia senala que el glaucoma hereditario en Costa Rica tiene una gran heterogeneidad gcnetica y que es muy posible que los estudios que se desarrollan vayan a descubrir nuevos genes involucrados en la patologiaGlaucoma 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 (GLCIA-GLCIF) and two genes (TIGRIMYOC and OPTN) arc involved in the development of juvenile (JOAG) and adult onset or chronic primary open angle glaucoma (COAG), while two loci (GLC3A,GLC313) and one gene (CYPIB1) 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 stale, 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 TIGIUMYOC 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 COAL families was chosen for a genome scan with 379 microsatellitc 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