Download Mutation analysis of bigH3 gene in patients with corneal dystrophy

SEARCH FOR THE GLAUCOMA GENES
CP Pang
Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong,
Hong Kong.
Glaucoma is a group of disorders of the optic nerves and a leading cause of vision loss,
affecting 2% of the world’s population and accounting for 15% of the world’s blindness.
Major primary forms of glaucoma, including primary open angle glaucoma (POAG), primary
close angle glaucoma (PCAG), and congenital glaucoma (PCG), can be familial or sporadic,
with heterogeneous genetics. Only a portion of glaucoma families show Mendelian pattern of
inheritance, mostly autosomal dominant. Some genes involved with ocular development, such
as PAX6, PITX2, and FOXC1, may have association with developmental glaucoma. PCG is
linked to the GLC3A locus on 2p21 and the GLC3B locus on 1p36. Deleterious mutations in
the CYP1B1 gene in the GLC3A locus have been found in about 50% of PCG patients. No
genetic locus has been identified for PCAG, but there is a possible site on chromosome 10.
For POAG, more than 10 chromosomal loci have been mapped. But there are only 2
confirmed genes, MYOC and OPTN. Over 60 MYOC mutations that cause glaucoma in 1.54.3% POAG patients in different populations have been identified, with the Q368Stop
harboring a founder effect in Caucasian patients. In one study on Caucasians, a defective
OPTN gene is linked to 16.7% of POAG families. We have shown MYOC is not required for
normal eye function. The disease causal effects of MYOC are mainly due to over-expressions
or gain of pathological function that disrupt aqueous outflow. We found lower frequencies of
MYOC and OPTN mutations in Chinese POAG patients, at 1-2%. Ethnic specific mutation
patterns of MYOC and OPTN exist in POAG. Our recent linkage analysis and whole genome
scan has indicated a putative site in chromosome 13.