advertisement
Abstract #121581 Published in IGR 25-1
Potential Involvements of Cilia-Centrosomal Genes in Primary Congenital Glaucoma
Pyatla G; Kabra M; Mandal AK; Zhang W; Mishra A; Bera S; Rathi S; Patnaik S; Anthony AA; Dixit R; Banerjee S; Shekhar K; Marmamula S; Kaur I; Khanna RC; Chakrabarti SInternational journal of molecular sciences 2024; 25:
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.
Full article