Authors’ response: Fragile X primary ovarian insufficiency
Keywords:
FMR1, Fragile X Syndrome, Primary ovarian insufficiency, Trinucleotide Repeat Expansion, Genetic Counseling, Infertility, FemaleArticle Sidebar
Main Article Content
Primary ovarian insufficiency (POI) is well documented in women carrying the premutation with alleles between 55 and 200 CGG triplets in the 5' untranslated region of the FMR1 gene; in these women, POI is found in 20% and is named Fragile X-associated Primary Ovarian insufficiency (FXPOI) compared to only 1% in women in the general population (1,2). However, in women with the full mutation, more than 200 repeats of the CGG triplet with or without intellectual disability the FXPOI has not been described. In the author's experience, of approximately 220 women with complete mutation, none had POI.
Now, we would propose that in those adolescent or young women with genetic diseases and/or congenital anomalies in whom the Mullerian anomalies like the absence of uterus and Turner syndrome have been ruled out, PCR with double or triple primer for the quantification of the triplets in the 5' untranslated region of the FMR1 gene should be performed to identify if they have a double genetic hit (4), the second hit being the FMR1 premutation (5).
Wilmar Saldarriaga, University of Valle
https://orcid.org/0000-0001-7815-4390
Universidad del Valle, Facultad de Salud, Escuela de Ciencias Básicas, Cali, Colombia.
Hospital Universitario del Valle “Evaristo García” E.S.E, Cali, Colombia.
Randi J. Hagerman, University of California, Davis
https://orcid.org/0000-0001-5029-8448
University of California, Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, Sacramento, CA, USA.
UC Davis Medical Center, Sacramento, CA, USA.
University of California, Department of Pediatrics, Davis, CA, USA.
1. Acero-Garcés DO, Saldarriaga W, Cabal-Herrera AM, Rojas CA, Hagerman RJ. Fragile X Syndrome in children. Colomb Med (Cali). 2023;54(2):e4005089. https://doi.org/10.25100/cm.v54i2.5089. PMID: 37664646; PMCID: PMC10469670.
2. Silvén H, Savukoski SM, Pesonen P, Pukkala E, Ojaniemi M, Gissler M, et al. Association of genetic disorders and congenital malformations with premature ovarian insufficiency: a nationwide register-based study. Hum Reprod. 2023;38(6):1224-30. https://doi.org/10.1093/humrep/dead066. PMID: 37018629; PMCID: PMC10233236.
3. Hipp HS, Charen KH, Spencer JB, Allen EG, Sherman SL. Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI). Menopause. 2016;23(9):993-9. https://doi.org/10.1097/GME.0000000000000658. PMID: 27552334; PMCID: PMC4998843.
4. Allen EG, Charen K, Hipp HS, Shubeck L, Amin A, He W, et al. Refining the risk for fragile X-associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size. Genet Med. 2021;23(9):1648-55. https://doi.org/10.1038/s41436-021-01177-y. PMID: 33927378; PMCID: PMC8460441.
5. Saldarriaga W, Payán-Gómez C, González-Teshima LY, Rosa L, Tassone F, Hagerman RJ. Double genetic hit: fragile X syndrome and partial deletion of protein patched homolog 1 antisense as cause of severe autism spectrum disorder. J Dev Behav Pediatr. 2020;41(9):724-8. https://doi.org/10.1097/DBP.0000000000000850. PMID: 32947579.
6. Lozano R, Hagerman RJ, Duyzend M, Budimirovic DB, Eichler EE, Tassone F. Genomic studies in fragile X premutation carriers. J Neurodev Disord. 2014;6(1):27. https://doi.org/10.1186/1866-1955-6-27. PMID: 25170347; PMCID: PMC4147387.
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