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Potential Involvements of Cilia-Centrosomal Genes in Primary Congenital Glaucoma

Goutham Pyatla1,2, Meha Kabra1, Anil K Mandal3

  • 1Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L.V. Prasad Eye Institute, Hyderabad 500034, Telangana, India.

International Journal of Molecular Sciences
|September 28, 2024
PubMed

Insights

Rare variants in CEP164 and INPP5E genes suggest cilia-centrosomal dysfunction in primary congenital glaucoma (PCG) pathogenesis. These findings may lead to new diagnostic and therapeutic strategies for PCG.

Area of Science:

  • Ophthalmology
  • Genetics
  • Cell Biology

Background:

  • Primary congenital glaucoma (PCG) is a rare childhood eye disease caused by developmental abnormalities.
  • Previous research linked PCG to variants in genes like CYP1B1, LTBP2, TEK, MYOC, FOXC1, and PRSS56.
  • Some implicated genes involve centrosomal or ciliary functions, hinting at a role for these cellular components.

Purpose of the Study:

  • To investigate the role of CEP164, a core centrosomal protein, in the pathogenesis of primary congenital glaucoma.
  • To explore the involvement of INPP5E, a synergistic interactor of CEP164, in PCG.
  • To analyze the genetic contribution of cilia-centrosomal pathways to PCG.

Main Methods:

  • Deep sequencing of CEP164 in a cohort of 298 PCG patients and 1757 controls.
  • Screening for pathogenic variants in INPP5E.
  • Assessing co-occurrence of CEP164 variants with other known PCG genes.
  • Investigating physical interaction between CEP164 and CYP1B1 proteins in HEK293 cells.

Main Results:

  • Rare pathogenic variants in CEP164 were identified in 5.36% of PCG cases.
  • Co-occurrence of CEP164 heterozygous alleles with other genes was observed in 1.34% of cases, associated with poorer prognosis.
  • Physical interaction between CEP164 and CYP1B1 was confirmed.
  • Pathogenic variants in INPP5E were found at a lower frequency (0.67%).

Conclusions:

  • CEP164 and INPP5E variants are potentially implicated in primary congenital glaucoma pathogenesis.
  • Cilia-centrosomal functions represent a novel area for PCG research.
  • Genetic interactions and protein interactions highlight the complexity of PCG etiology.

Keywords:
CEP164CYP1B1INPP5Eanterior segmentcentrosomeciliageneintraocular pressureprimary congenital glaucoma

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