The FMR1 premutation and reproduction

Wittenberger, Michael D.; Hagerman, Randi J.; Sherman, Stephanie L.; McConkie‐Rosell, Allyn; Welt, Corrine K.; Rebar, Robert W.; Corrigan, Emily C.; Simpson, Joe Leigh; Nelson, Lawrence M.

doi:10.1016/j.fertnstert.2006.09.004

Cited by 375 publications

(317 citation statements)

References 101 publications

(126 reference statements)

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“…The relevance of expanded CGG repeat lengths in otherwise symptom-free carrier women not only resides in transmitting the full mutation to the male offspring, but also in the proportional expansion of intermediate and premutational CGG repeat numbers transmitted to the X chromosome of the female progeny 1 and in fragile X-associated primary ovarian insufficiency (POI). 2 Considering the severity of the syndrome, the frequency of the carrier status and the potential long-term benefits to the daughters knowing about their mother's screening result, the installment of population-based screening programs has been advocated repeatedly. [3][4][5] In addition, carrier status testing would also enable women into timely reproductive planning.…”

Section: Introductionmentioning

confidence: 99%

Similar prevalence of expanded CGG repeat lengths in the fragile X mental retardation I gene among infertile women and among women with proven fertility: a prospective study

Geyter

M’Rabet

Geyter

et al. 2014

Genetics in Medicine

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Section: Introductionmentioning

confidence: 99%

Similar prevalence of expanded CGG repeat lengths in the fragile X mental retardation I gene among infertile women and among women with proven fertility: a prospective study

Geyter

M’Rabet

Geyter

et al. 2014

Genetics in Medicine

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“…Overall, carriers have been proven to go through menopause approximately 5 years earlier than controls [17] and also to be at increased risk for primary ovarian insufficiency [18]. Approximately 3% of female carriers have their final menses before age 29 and 1% prior to age 18 [19].…”

Section: Reproductive Involvementmentioning

confidence: 99%

“…Primary ovarian insufficiency was one of the first conditions ever to be associated with carrier women. It has an approximate prevalence of 16% [20], and the exact pathophysiologic mechanism underlying its cause is presently unknown, although it is suggested that it might be caused by an RNAtoxic effect [18,21].…”

Section: Reproductive Involvementmentioning

confidence: 99%

“…Their overall conclusion was that those carriers of premutations ranging from 80-99 CGG repeats have increased rates of menstrual dysfunction, reduction in age of menopause, infertility, dizygotic twinning, and POI when compared to non-carriers, but most importantly, carriers of low and high premutation repeats also suffer from certain degrees of ovarian insufficiency, just not to such an extent as medium-sized carriers. This is important since it leads to the hypothesis that women with premutations may have a continuum of impaired ovarian function [18], being POI one tail of the distribution and relating to the number of CGG repeats present in the FMR1 gene.…”

Section: Reproductive Involvementmentioning

confidence: 99%

See 1 more Smart Citation

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency

Hoyos

Thakur

2016

J Assist Reprod Genet

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Fragile X premutation carriers have 55-200 CGG repeats in the 5' untranslated region of the FMR1 gene. Women with this premutation face many physical and emotional challenges in their life. Approximately 20% of these women will develop fragile X-associated primary ovarian insufficiency (FXPOI). In addition, they suffer from increased rates of menstrual dysfunction, diminished ovarian reserve, reduction in age of menopause, infertility, dizygotic twinning, and risk of having an offspring with a premutation or full mutation. Consequent chronic hypoestrogenism may result in impaired bone health and increased cardiovascular risk. Neuropsychiatric issues include risk of developing fragile X-associated tremor/ataxia syndrome, neuropathy, musculoskeletal problems, increased prevalence of anxiety, depression, and sleep disturbances independent of the stress of raising an offspring with fragile X syndrome and higher risk of postpartum depression. Some studies have reported a higher prevalence of thyroid abnormalities and hypertension in these women. Reproductive health providers play an important role in the health supervision of women with fragile X premutation. Awareness of these risks and correlation of the various manifestations could help in early diagnosis and coordination of care and services for these women and their families. This paper reviews current evidence regarding the possible conditions that may present in women with premutation-sized repeats beyond FXPOI.

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“…Female carriers have up to a 50 % risk of having a child with FXS. There are also health implications for carriers of the premutation : females are at risk of fertility problems and early menopause (Wittenberger et al 2007), a condition referred to as fragile X-associated primary ovarian insufficiency (McConkie-Rosell et al 2007), and males, and to a lesser extent females, may develop fragile Xassociated tremor-ataxia syndrome (FXTAS), a late-onset neurodegenerative condition (Hagerman et al 2001). Further research will assist in fully understanding the significance of intermediate alleles (45)(46)(47)(48)(49)(50)(51)(52)(53)(54) identified in the general population; however, any screening program would need to have strategies in place to manage these results (Archibald et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“It gives them more options”: preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare

et al. 2016

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This study aims to explore stakeholder views about offering population-based genetic carrier screening for fragile X syndrome. A qualitative study using interviews and focus groups with stakeholders was undertaken to allow for an indepth exploration of views and perceptions about practicalities of, and strategies for, offering carrier screening for fragile X syndrome to the general population in healthcare settings. A total of 188 stakeholders took part including healthcare providers (n = 81), relatives of people with fragile X syndrome (n = 29), and members of the general community (n = 78). The importance of raising community awareness about screening and providing appropriate support for carriers was emphasized. There was a preference for preconception carrier screening and for providing people with the opportunity to make an informed decision about screening. Primary care was highlighted as a setting which would ensure screening is accessible; however, challenges of offering screening in primary care were identified including time to discuss screening, knowledge about the test and possible outcomes, and the health professionals' approach to offering screening. With the increasing availability of genetic carrier tests, it is essential that research now focuses on evaluating approaches for the delivery of carrier screening programs. Primary healthcare is perceived as an appropriate setting through which to access the target population, and raising awareness is essential to making genetic screening more accessible to the general community.

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The FMR1 premutation and reproduction

Cited by 375 publications

References 101 publications

Similar prevalence of expanded CGG repeat lengths in the fragile X mental retardation I gene among infertile women and among women with proven fertility: a prospective study

Similar prevalence of expanded CGG repeat lengths in the fragile X mental retardation I gene among infertile women and among women with proven fertility: a prospective study

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency

“It gives them more options”: preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare

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