Potential Involvements of Cilia-Centrosomal Genes in Primary Congenital Glaucoma.

Primary congenital glaucoma (PCG) occurs in children due to developmental abnormalities in the trabecular meshwork and anterior chamber angle. Previous studies have implicated rare variants in , , and and their interactions with , , and in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes () and perform ciliary functions (), we explored the involvement of a core centrosomal protein, , which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of with other genes were seen in four cases (1.34%), and a physical interaction was noted for CEP164 and CYP1B1 in HEK293 cells. Cases of co-harboring alleles of the and other genes had a poor prognosis compared with those with a single copy of the allele. We also screened , which synergistically interacts with , and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of and and the yet unexplored cilia-centrosomal functions in PCG pathogenesis.