title: BRCA1/2 mutations and FMR1 alleles are randomly distributed: a case control study.
abstract: BRCA mutation carriers were reported to display a skewed distribution of FMR1 genotypes, predominantly within the low normal range (CGG repeat number <26). This observation led to the interpretation that BRCA1/2 mutations are embryo-lethal, unless rescued by 'low FMR1 alleles'. We undertook to re-explore the distribution of FMR1 alleles subdivided into low, normal and high (<26, 26-34, and >34 CGG repeats, respectively) subgenotypes, on a cohort of 125 Ashkenazi women, carriers of a BRCA1/2 founder mutation. Ashkenazi healthy females (n=368), tested in the frame of the Israeli screening population program, served as controls. BRCA1/2 carriers and controls demonstrated a comparable and non-skewed FMR1 subgenotype distribution. Taken together, using a homogeneous ethnic group of Ashkenazi BRCA1/2 mutation carriers, we could not confirm the reported association between FMR1 low genotypes and BRCA1/2 mutations. The notion that BRCA1/2 mutations are embryo-lethal unless rescued by the low FMR1 subgenotypes is hereby refuted.
authors.affiliation: 1] Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel [2] Department of Nursing, University of Haifa, Haifa, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Dagan
authors.affiliation: 1] IVF Unit, Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.affiliation: 1] Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel [2] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Mory
authors.affiliation: The Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, Haifa, Israel.
authors.forename: Vardit
authors.initials: V
authors.lastname: Adir
authors.affiliation: 1] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel [2] The Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, Haifa, Israel.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Borochowitz
authors.affiliation: IVF Unit, Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Raanani
authors.affiliation: 1] Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel [2] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Kurolap
authors.affiliation: 1] Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel [2] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Melikhan-Revzin
authors.affiliation: 1] IVF Unit, Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel [2] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Meirow
authors.affiliation: 1] Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel [2] The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Baruch
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D017384:Sequence Deletion
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