Toward Primary Congenital Glaucoma GLC3B Gene Identification: The Case of Kazrin Gene

Primary Congenital Glaucoma (PCG) is an ocular disease that occurs before the age of 3 years, and results from malformation of the anterior eye chamber. To date, three chromosomal loci, GLC3A (2p21), GLC3B (1p36), and GLC3C (14q24) associated with PCG are reported. CYP1B1 and LTBP2 located on GLC3A and GLC3B, respectively, are the genes harboring mutations in PCG, however the PCG-associated gene within GLC3B is still unknown. In a previous study and using homozygosity mapping, we reported that GLC3B locus might be responsible for PCG in 30 % of Moroccan patients. Here, were aims to identify the PCG-associate gene within the GLC3B locus. Integrative analysis of genomic databases and using the GeneDistiller software was performed to identify potential PCG-associated genes in the GLC3B locus. Based on these analyses, KAZN gene was identified as a strong candidate gene given its position in the GLC3B susceptibility interval (KAZN exons 1 to 4 out of 17 overlap the GLC3B locus) and its role in morphogenesis of embryonic tissue and cells adhesion. Exons 1-4 of KAZN were amplified, sequenced and analyzed in homozygote patients for the GLC3B locus. No sequence variation was found in the four exons of homozygote patients for the GLC3B locus. This study suggest a priori no involvement of KAZN gene in PCG within Moroccan population, a total sequencing of KAZN gene may removes entirely this probability. Further research are also needed to discover the GLC3B locus causal gene responsible for PCG