Editing Fragile X syndrome (section)

=== Fertility ===
About 20% of women who are carriers for the fragile X premutation are affected by [[Fragile X-associated primary ovarian insufficiency]] (FXPOI), which is defined as premature [[menopause]], which is menopause occurring before 40 years of age (average age at menopause is 51 years old in the US).<ref name=Santoro>{{cite journal | vauthors = Santoro MR, Bray SM, Warren ST | title = Molecular mechanisms of fragile X syndrome: a twenty-year perspective | journal = Annual Review of Pathology | volume = 7 | pages = 219–245 | year = 2012 | pmid = 22017584 | doi = 10.1146/annurev-pathol-011811-132457 }}</ref><ref name=Peprah>{{cite journal | vauthors = Peprah E | title = Fragile X syndrome: the FMR1 CGG repeat distribution among world populations | journal = Annals of Human Genetics | volume = 76 | issue = 2 | pages = 178–191 | date = March 2012 | pmid = 22188182 | pmc = 3288311 | doi = 10.1111/j.1469-1809.2011.00694.x }}</ref> The number of CGG repeats correlates with [[penetrance]] and age of onset, but it is not a linear relationship.<ref>{{cite journal | vauthors = Sullivan AK, Marcus M, Epstein MP, Allen EG, Anido AE, Paquin JJ, Yadav-Shah M, Sherman SL | display-authors = 6 | title = Association of FMR1 repeat size with ovarian dysfunction | journal = Human Reproduction | volume = 20 | issue = 2 | pages = 402–412 | date = February 2005 | pmid = 15608041 | doi = 10.1093/humrep/deh635 | doi-access = free }}</ref><ref name=Santoro/> However [[premature menopause]] is more common in premutation carriers than in women with the full mutation, and the highest risk for FXPOI is observed in women with between 70-100 repeats.<ref>{{cite journal | vauthors = Allen EG, Charen K, Hipp HS, Shubeck L, Amin A, He W, Nolin SL, Glicksman A, Tortora N, McKinnon B, Shelly KE, Sherman SL | display-authors = 6 | title = Refining the risk for fragile X-associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size | language = English | journal = Genetics in Medicine | volume = 23 | issue = 9 | pages = 1648–1655 | date = September 2021 | pmid = 33927378 | pmc = 8460441 | doi = 10.1038/s41436-021-01177-y }}</ref><ref name=Bibi>{{cite journal | vauthors = Bibi G, Malcov M, Yuval Y, Reches A, Ben-Yosef D, Almog B, Amit A, Azem F | display-authors = 6 | title = The effect of CGG repeat number on ovarian response among fragile X premutation carriers undergoing preimplantation genetic diagnosis | journal = Fertility and Sterility | volume = 94 | issue = 3 | pages = 869–874 | date = August 2010 | pmid = 19481741 | doi = 10.1016/j.fertnstert.2009.04.047 | doi-access = free }}</ref> FXPOI is one of three Fragile X-associated Disorders (FXD) caused by changes in the FMR1 gene. FXPOI affects female premutation carriers, of which is caused by the FMR1 gene, when their ovaries are not functioning properly. Women with FXPOI may exhibit changes in menstrual cycles and have changes in hormone levels but not be considered menopausal. Women with FXPOI still have the chance to get pregnant in about 10% of cases, because their ovaries occasionally release viable [[Egg cell|eggs]] through "escape" ovulation.<ref>{{cite journal | vauthors = Sherman SL, Curnow EC, Easley CA, Jin P, Hukema RK, Tejada MI, Willemsen R, Usdin K | display-authors = 6 | title = Use of model systems to understand the etiology of fragile X-associated primary ovarian insufficiency (FXPOI) | journal = Journal of Neurodevelopmental Disorders | volume = 6 | issue = 1 | pages = 26 | date = 2014 | pmid = 25147583 | pmc = 4139715 | doi = 10.1186/1866-1955-6-26 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hipp HS, Charen KH, Spencer JB, Allen EG, Sherman SL | title = Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI) | journal = Menopause | volume = 23 | issue = 9 | pages = 993–999 | date = September 2016 | pmid = 27552334 | pmc = 4998843 | doi = 10.1097/GME.0000000000000658 }}</ref>

[[FMR1|FMRP]] is a [[chromatin]]-binding protein that functions in the [[DNA damage (naturally occurring)|DNA damage]] response.<ref name="pmid24813610">{{cite journal | vauthors = Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stützer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y | display-authors = 6 | title = A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response | journal = Cell | volume = 157 | issue = 4 | pages = 869–881 | date = May 2014 | pmid = 24813610 | pmc = 4038154 | doi = 10.1016/j.cell.2014.03.040 }}</ref><ref name="pmid29796988">{{cite journal | vauthors = Dockendorff TC, Labrador M | title = The Fragile X Protein and Genome Function | journal = Molecular Neurobiology | volume = 56 | issue = 1 | pages = 711–721 | date = January 2019 | pmid = 29796988 | doi = 10.1007/s12035-018-1122-9 | s2cid = 44159474 }}</ref> FMRP also occupies sites on [[meiosis|meiotic]] [[chromosome]]s and regulates the dynamics of the DNA damage response machinery during [[spermatogenesis]].<ref name="pmid24813610" />