Candidate Gene Analysis Identifies Mutations in CYP1B1 and LTBP2 in Indian Families with Primary Congenital Glaucoma

Genet Test Mol Biomarkers. 2017 Apr;21(4):252-258. doi: 10.1089/gtmb.2016.0203. Epub 2017 Feb 27.

Abstract

Background: Primary congenital glaucoma (PCG) is a severe ocular disorder that presents early in life. Cytochrome P4501B1 (CYP1B1) and latent transforming growth factor-beta-binding protein 2 (LTBP2) are the most commonly mutated genes in PCG.

Aim: To investigate the causative genetic mutations in eight Indian families with PCG.

Materials and methods: Whole-exome sequencing was applied to analyze the genomic DNA samples from PCG probands. Sanger sequencing was utilized to confirm the identified mutations.

Results: We identified four homozygous missense mutations (c.1405C>T, p.R469W; c.1397G>T, p.G466V; c.1198C>T, p.P400S; and c.1103G>A, p.R368H) in CYP1B1 and one nonsense mutation (c.2421G>A, p.W807X) in LTBP2 in eight Indian families. Among the five mutations identified, G466V in CYP1B1 and W807X in LTBP2 represent novel mutations.

Conclusions: Our study expands the mutational spectrum of PCG in the Indian population.

Keywords: CYP1B1; LTBP1; primary congenital glaucoma.

MeSH terms

  • Adult
  • Asian People / genetics
  • Child
  • Child, Preschool
  • Consanguinity
  • Cytochrome P-450 CYP1B1 / genetics*
  • Cytochrome P-450 CYP1B1 / metabolism
  • DNA Mutational Analysis
  • Eye Proteins / genetics
  • Female
  • Genetic Association Studies
  • Genome-Wide Association Study
  • Glaucoma / genetics*
  • Haplotypes
  • Humans
  • India
  • Infant
  • Latent TGF-beta Binding Proteins / genetics*
  • Latent TGF-beta Binding Proteins / metabolism
  • Male
  • Mutation, Missense / genetics
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • Eye Proteins
  • LTBP2 protein, human
  • Latent TGF-beta Binding Proteins
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1