title: FMR1 CGG allele length in Israeli BRCA1/BRCA2 mutation carriers and the general population display distinct distribution patterns.
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.
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, and theGyneco-oncology Department,Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University,Ramat AvivIsrael.
authors.forename: Yael
authors.initials: Y
authors.lastname: Laitman
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, and theGyneco-oncology Department,Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University,Ramat AvivIsrael.
authors.forename: Liat
authors.initials: L
authors.lastname: Ries-Levavi
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, and theGyneco-oncology Department,Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University,Ramat AvivIsrael.
authors.forename: Michal
authors.initials: M
authors.lastname: Berkensdadt
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, and theGyneco-oncology Department,Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University,Ramat AvivIsrael.
authors.forename: Jacob
authors.initials: J
authors.lastname: Korach
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, and theGyneco-oncology Department,Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University,Ramat AvivIsrael.
authors.forename: Tamar
authors.initials: T
authors.lastname: Perri
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, and theGyneco-oncology Department,Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University,Ramat AvivIsrael.
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.affiliation: Susanne Levy Gertner Oncogenetics Unit,The Danek Gertner Institute of Human Genetics, and theGyneco-oncology Department,Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University,Ramat AvivIsrael.
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D016649:Primary Ovarian Insufficiency / Q000208:ethnology* / Q000235:genetics*; D018709:Statistics, Nonparametric; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C497683:FMR1 protein, human