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

Autor: Pyatla G; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India.; Manipal Academy of Higher Education, Manipal 576104, Karnataka, India., Kabra M; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Mandal AK; Jasti V Ramanamma Children's Eye Care Centre, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Zhang W; Department of Ophthalmology, UMASS Medical School, Worcester, MA 01605, USA., Mishra A; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India.; Manipal Academy of Higher Education, Manipal 576104, Karnataka, India., Bera S; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India.; Manipal Academy of Higher Education, Manipal 576104, Karnataka, India., Rathi S; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Patnaik S; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Anthony AA; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Dixit R; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Banerjee S; Gullapalli Pratibha Rao International Centre for Advancement of Rural Eye Care, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Shekhar K; Gullapalli Pratibha Rao International Centre for Advancement of Rural Eye Care, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Marmamula S; Gullapalli Pratibha Rao International Centre for Advancement of Rural Eye Care, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Kaur I; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Khanna RC; Gullapalli Pratibha Rao International Centre for Advancement of Rural Eye Care, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India., Chakrabarti S; Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Sep 18; Vol. 25 (18). Date of Electronic Publication: 2024 Sep 18.
DOI: 10.3390/ijms251810028
Abstrakt: 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 CYP1B1 , LTBP2 , and TEK and their interactions with MYOC , FOXC1 , and PRSS56 in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes ( MYOC ) and perform ciliary functions ( TEK ), we explored the involvement of a core centrosomal protein, CEP164 , which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of CEP164 in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed CEP164 rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of CEP164 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 CEP164 and other genes had a poor prognosis compared with those with a single copy of the CEP164 allele. We also screened INPP5E , which synergistically interacts with CEP164 , and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of CEP164 and INPP5E and the yet unexplored cilia-centrosomal functions in PCG pathogenesis.
Databáze: MEDLINE
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