Primary congenital glaucoma due to paternal uniparental isodisomy of chromosome 2 and CYP1B1 deletion

Mol Genet Genomic Med. 2019 Aug;7(8):e774. doi: 10.1002/mgg3.774. Epub 2019 Jun 28.

Abstract

Background: CYP1B1 variants and deletions are the most common cause of primary congenital glaucoma (PCG).

Methods: We investigated an individual with PCG from the Australian and New Zealand Registry of Advanced Glaucoma. We performed sequencing of the CYP1B1 gene, followed by Multiplex Ligation-dependent Probe Amplification and SNP array.

Results: We identified a homozygous deletion of the CYP1B1 gene by Multiplex Ligation-dependent Probe Amplification and confirmed that the father was heterozygous for a CYP1B1 deletion but the mother had normal gene copy number. SNP array identified paternal uniparental isodisomy of the entire chromosome 2.

Conclusions: This study is the first report of a homozygous CYP1B1 whole gene deletion due to paternal uniparental isodisomy of chromosome 2 as a cause of PCG. These results illustrate the importance of genetic testing in providing appropriate genetic counseling regarding the risks of recurrence.

Keywords: CYP1B1; childhood glaucoma; chromosome 2; gene deletion; primary congenital glaucoma; uniparental disomy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Australia
  • Chromosomes, Human, Pair 2*
  • Cytochrome P-450 CYP1B1 / genetics*
  • Exons
  • Gene Deletion
  • Gene Dosage
  • Genetic Predisposition to Disease / genetics*
  • Glaucoma / congenital*
  • Glaucoma / diagnostic imaging
  • Glaucoma / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Pedigree
  • Uniparental Disomy / genetics*

Substances

  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1