BRCA1/2 mutations and FMR1 alleles are randomly distributed: a case control study |
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| Authors: | Efrat Dagan Yoram Cohen Adi Mory Vardit Adir Zvi Borochowitz Hila Raanani Alina Kurolap Svetlana Melikhan-Revzin Dror Meirow Ruth Gershoni-Baruch |
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| Institution: | 1.Institute of Human Genetics, Rambam Health Care Campus, Haifa, Israel;2.Department of Nursing, University of Haifa, Haifa, Israel;3.IVF Unit, Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel;4.Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;5.The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel;6.The Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, Haifa, Israel |
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| 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. |
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| Keywords: | FMR1 subgenotypes CGG repeats BRCA1/2 |
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