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Updated: May 10, 2026
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
FMR1 low sub-genotype does not rescue BRCA1/2-mutated human embryos and does not explain primary ovarian
R D Brandão1, K van Roozendaal, D Tserpelis
1Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht, The Netherlands. rita.brandao@maastrichtuniversity.nl
Study Question:
Can we confirm in our population whether FMRI low sub-genotypes are associated with BRCA1/2 mutations, as recently proposed?
Summary Answer:
Our results indicate that the distribution of the FMR1 sub-genotypes in female BRCA1/2-mutation carriers is significantly different from what has been reported previously and resembles that of the control population. FMRI low sub-genotypes are not associated with BRCA1/2 mutations and this association is also absent among male mutation carriers.
What Is Known Already:
Recently, BRCA1 mutations were reported to be associated with primary ovarian insufficiency (POI) in female carriers. In animal models, BRCA2-deficiency also results in impaired oogenesis. A recent study has reported that the POI in BRCA1/2-mutation carriers is most likely due to low FMR1 sub-genotype (CGG n < 26) and the authors also suggested that low sub-genotypes of the FMR1 gene might be important to rescue the BRCA1/2 embryos, which would otherwise be embryonically-lethal.
Study Design, Size, Duration:
This retrospective study was performed in October and November of 2012, using genetic material of 464 patients who underwent genetic screening in our centre in the past.
Participants/Materials, Setting, Methods:
We tested the FMR1 sub-genotypes in 60 female and 29 males with either BRCA1 or BRCA2 mutations and 375 controls by PCR amplification and size fragment analysis.
Main Results:
We did not find any evidence for an association of FMR1 low sub-genotypes and BRCA1/2 mutations.
Limitations, Reasons For Caution:
This association study assumes that the female BRCA1/2 population tested has POI.
Wider Implications Of The Findings:
Low FMR1 sub-genotypes are not responsible for the presumed rescue of embryos with BRCA1/2 mutations. Furthermore, the molecular mechanism of the POI in BRCA1/2-female carriers is not likely to be associated with low FMR1 sub-genotype.
Study Funding/Competing Interest(S):
The Department of Clinical Genetics of the Maastricht University Medical Centre supported the study. The authors do not have any competing interests to declare.
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