Mutated MCM9 is associated with predisposition to hereditary mixed polyposis and colorectal cancer in addition to primary ovarian failure

Cancer Genet. 2015 Dec;208(12):621-4. doi: 10.1016/j.cancergen.2015.10.001. Epub 2015 Oct 22.

Abstract

Mutations in MCM9, which encodes DNA helicase, were recently shown to cause a clinical phenotype of primary ovarian failure and chromosomal instability. MCM9 plays an essential role in homologous recombination-mediated double-strand break repair. We describe a multiplex family with early colorectal carcinoma and mixed polyposis associated with primary hypergonadotropic hypogonadism. A combination of whole genome homozygosity mapping as well as exome sequencing and targeted gene sequencing identified a homozygous c.672_673delGGinsC mutation that predicts a truncated protein, p.Glu225Lysfs*4. Our data expand the phenotypic spectrum of MCM9 mutations and suggest a link between MCM9 and inherited predisposition to mixed polyposis and early-onset colorectal cancer.

Keywords: DNA helicase MCM9; chromosomal instability; colorectal cancer; hereditary mixed polyposis; primary ovarian failure.

Publication types

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

MeSH terms

  • Adenomatous Polyposis Coli* / complications
  • Adenomatous Polyposis Coli* / genetics
  • Adult
  • Chromosomal Instability
  • Colorectal Neoplasms* / complications
  • Colorectal Neoplasms* / genetics
  • Consanguinity
  • Female
  • Humans
  • Minichromosome Maintenance Proteins / genetics*
  • Mutation
  • Pedigree
  • Primary Ovarian Insufficiency* / complications
  • Primary Ovarian Insufficiency* / genetics

Substances

  • MCM9 protein, human
  • Minichromosome Maintenance Proteins