Department of Clinical Genetics, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht, The Netherlands.
Hum Reprod. 2013 Aug;28(8):2308-11. doi: 10.1093/humrep/det254. Epub 2013 Jun 11.
Can we confirm in our population whether FMRI low sub-genotypes are associated with BRCA1/2 mutations, as recently proposed?
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.
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.
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.
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.
我们能否在我们的人群中证实，正如最近提出的那样，FMRI 低亚基因型与 BRCA1/2 突变有关？
我们的结果表明，女性 BRCA1/2 突变携带者中 FMR1 亚基因型的分布与先前报道的明显不同，与对照人群相似。FMRI 低亚基因型与 BRCA1/2 突变无关，男性突变携带者中也不存在这种关联。
最近，BRCA1 突变与女性携带者的原发性卵巢功能不全（POI）有关。在动物模型中，BRCA2 缺陷也导致卵母细胞生成受损。最近的一项研究报告称，BRCA1/2 突变携带者的 POI 很可能是由于 FMR1 低亚基因型（CGG n < 26）引起的，作者还提出，FMR1 基因的低亚基因型可能对挽救否则会胚胎致死的 BRCA1/2 胚胎很重要。
研究设计、规模、持续时间：本回顾性研究于 2012 年 10 月至 11 月进行，使用过去在我们中心进行基因筛查的 464 名患者的遗传物质。
参与者/材料、地点、方法：我们通过 PCR 扩增和大小片段分析，测试了 60 名女性和 29 名男性 BRCA1 或 BRCA2 突变患者以及 375 名对照者的 FMR1 亚基因型。
我们没有发现 FMR1 低亚基因型与 BRCA1/2 突变之间存在任何关联的证据。
局限性、谨慎的原因：这项关联研究假设所测试的女性 BRCA1/2 人群患有 POI。
低 FMR1 亚基因型与 BRCA1/2 突变胚胎的假定拯救无关。此外，BRCA1/2 女性携带者中 POI 的分子机制不太可能与低 FMR1 亚基因型有关。
研究资金/竞争利益：马斯特里赫特大学医学中心的临床遗传学系为该研究提供了支持。作者没有任何竞争利益需要申报。
