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. 2023 Mar;40(3):683-688.
doi: 10.1007/s10815-023-02730-1. Epub 2023 Feb 1.

The association between a carrier state of FMR1 premutation and numeric sex chromosome variations

Mira Malcov  1 , Ophir Blickstein  1 , Dana Brabbing-Goldstein  2 , Adi Reches  1   2 , Yael Kalma  1 , Yuval Fouks  1   3 , Foad Azem  1 , Yoni Cohen  4
Affiliations

The association between a carrier state of FMR1 premutation and numeric sex chromosome variations

Mira Malcov et al. J Assist Reprod Genet. 2023 Mar.

Abstract

Purpose: Women carriers of FMR1 premutation are at increased risk of early ovarian dysfunction and even premature ovarian insufficiency. The aim of this study was to examine a possible association between FMR1 permutation and numeric sex chromosome variations.

Methods: A retrospective case-control study conducted in the reproductive center of a university-affiliated medical center. The primary outcome measure was the rate of sex chromosomal numerical aberrations, as demonstrated by haplotype analyses, in FMR1 premutation carriers compared to X-linked preimplantation genetic testing for monogenic/single gene defect (PGT-M) cycles for other indications that do not affect the ovarian follicles and oocytes.

Results: A total of 2790 embryos with a final genetic analysis from 577 IVF PGT-M cycles were included in the final analysis. Mean age was similar between the groups, however, FMR1 carriers required more gonadotropins, and more women were poor responders with three or less oocytes collected. The ratio of embryos carrying a numeric sex chromosome variation was similar: 8.3% (138/1668) of embryos in the FMR1 group compared to 7.1% (80/1122) in the controls. A subgroup analysis based on age and response to stimulation has not demonstrated a significant difference either.

Conclusions: Although carriers of FMR1 premutation exhibit signs of reduced ovarian response, it does not seem to affect the rate of numeric sex chromosomal variation compared to women undergoing PGT-M for other indications. This suggests that the mechanism for chromosomal number aberrations in women at advanced maternal age are different to those FMR1 premutation carriers with poor ovarian reserve.

Keywords: Aneuploidy; FMR-1; Ovarian reserve; PGT-M; Sex chromosome aneuploidies.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

References

    1. Tassone F, Iong KP, Tong TH, Lo J, Gane LW, Berry-Kravis E, et al. FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States. Genome Med. 2012;4(12):100. doi: 10.1186/gm401. - DOI - PMC - PubMed
    1. American College of Obstetricians and Gynecologists Committee opinion No. 691: carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41–e55. doi: 10.1097/AOG.0000000000001952. - DOI - PubMed
    1. Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell. 1991;66(4):817–822. doi: 10.1016/0092-8674(91)90125-i. - DOI - PubMed
    1. Tassone F, Hagerman RJ, Taylor AK, Mills JB, Harris SW, Gane LW, et al. Clinical involvement and protein expression in individuals with the FMR1 premutation. Am J Med Genet. 2000;91(2):144–152. doi: 10.1002/(sici)1096-8628(20000313)91:2. - DOI - PubMed
    1. Elizur SE, Lebovitz O, Derech-Haim S, Dratviman-Storobinsky O, Feldman B, Dor J, et al. Elevated levels of FMR1 mRNA in granulosa cells are associated with low ovarian reserve in FMR1 premutation carriers. PLoS One. 2014;9(8):e105121. doi: 10.1371/journal.pone.0105121. - DOI - PMC - PubMed

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