FMR1 CGG allele length in Israeli BRCA1/BRCA2 mutation carriers and the general population display distinct distribution patterns

Genet Res (Camb). 2014 Oct 8:96:e11. doi: 10.1017/S0016672314000147.

Abstract

Premature ovarian failure and diminished ovarian reserve have been noted both in female BRCA1/BRCA2 mutation carriers and in carriers of the Fragile X syndrome FMR1 gene CGG repeat size premutation. Based on the observation that BRCA mutation carriers do not harbour long CGG repeats in the FMR1 gene, it was hypothesized that BRCA-associated premature ovarian failure is mediated via FMR1. To test this notion, we evaluated the distribution of constitutional FMR1 genotypes in 188 BRCA1/BRCA2 mutation-positive Jewish Ashkenazi women and 15 708 female, mostly Ashkenazi controls in Israel. BRCA1/BRCA2 mutation carriers displayed a unique distribution of FMR1 genotypes compared with controls (p = 0·018) with a prominence of the shorter CGG alleles (<26 repeats). There was no allele size distribution differences within BRCA carriers when comparing cancer free (n = 95) and breast cancer affected women (n = 93) (p = 0·43). In conclusion, BRCA mutation carriers exhibit a distinct CGG FMR1 repeat size pattern compared with the general population, but it is unlikely to account for the reported diminished ovarian reserve or act as a modifier breast cancer gene in BRCA mutation carriers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Genotype
  • Humans
  • Israel / epidemiology
  • Jews / genetics*
  • Mutation / genetics
  • Primary Ovarian Insufficiency / ethnology*
  • Primary Ovarian Insufficiency / genetics*
  • Statistics, Nonparametric
  • Trinucleotide Repeats / genetics

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • FMR1 protein, human
  • Fragile X Mental Retardation Protein