Examination of reproductive aging milestones among women who carry the FMR1premutation

Allen, Emily G.; Sullivan, Amy K.; Marcus, Michele; Small, Chanley M.; Dominguez, Celia E.; Epstein, Michael P.; Charen, Krista; He, Weiya; Taylor, Kira C.; Sherman, Stephanie L.

doi:10.1093/humrep/dem148

Cited by 205 publications

(235 citation statements)

References 44 publications

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“…The interesting fact about this finding is that it has also been reported for ovarian insufficiency [21][22][23][24].…”

Section: Neuropsychiatric and Muscular Involvementsupporting

confidence: 63%

“…Besides Allen et al (2007) [24], other investigators have also reported a continuum of impaired ovarian function. Welt et al (2004) [25] recruited 11 women with the premutation and compared them with age-matched controls in order to show differences in menstrual cycles and hormonal changes.…”

Section: Reproductive Involvementmentioning

confidence: 99%

“…It has been found that the risk of POI and the ovarian manifestations present on a specific patient may have a non-linear association with the number of CGG repeats, with the risk of developing ovarian insufficiency increasing with the number of repeats and then reaching a plateau or even decreasing after 80-100 CGG repeats are reached [21][22][23][24]. Allen et al (2007) [24] did a study with 948 carriers with varying repeat sizes in order to get a better view of the reproductive aging milestones among these women and its relation with the number of CGG repeats present. To accomplish this, the author classified the subjects into non-carriers (<59), low (59-79), medium (80-100), and high premutation alleles (>100 repeats) and compared the prevalence of POI between non-carriers and the other premutation groups.…”

Section: Reproductive Involvementmentioning

confidence: 99%

See 2 more Smart Citations

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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“…The interesting fact about this finding is that it has also been reported for ovarian insufficiency [21][22][23][24].…”

Section: Neuropsychiatric and Muscular Involvementsupporting

confidence: 63%

Section: Reproductive Involvementmentioning

confidence: 99%

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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“…When there is a full mutation, the gene is silenced by methylation, resulting in the absence of FMR protein (FMRP) expression, which causes mental retardation. Premutations of FMR1 gene, especially those with ~8099 repeats, are the most common discovered genetic cause of spontaneous 46, XX POI, and the resultant POI is named the fragile X-related primary ovarian insufficiency (FXPOI) [6,17,22,32]. Premutation alleles remain unmethylated, and lead to increased FMR1 transcription and decreased levels of FMRP [22].…”

Section: Poi Genes On X Chromosomementioning

confidence: 99%

An update on primary ovarian insufficiency

Jin

Huang

2012

Sci. China Life Sci.

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Primary ovarian insufficiency (POI) occurs in about 1% of female population under the age of 40, leading to reproductive problems, an earlier encounter with menopausal symptoms, and complicated diseases. There are three presumable mechanisms involved in the development of POI, namely apoptosis acceleration, follicular maturation blocking and premature follicle activation, through the following studied causes: (i) chromosomal abnormalities or gene mutations: mostly involve X chromosome, such as FMR1 premutation; more and more potentially causal genes have been screened recently; (ii) metabolic disorders such as classic galactosaemia and 17-OH deficiency; (iii) autoimmune mediated ovarian damage: observed alone or with some certain autoimmune disorders and syndromes; but the specificity and sensitivity of antibodies towards ovary are still questionable; (iv) iatrogenic: radiotherapy or chemotherapy used in cancer treatment, as well as pelvic surgery with potential threat to ovaries' blood supply can directly damage ovarian function; (v) virus infection such as HIV and mumps; (vi) toxins and other environmental/lifestyle factors: cigarette smoking, toxins (e.g., 4-vinylcyclohexene diepoxide), and other environmental factors are associated with the development of POI. The etiology of a majority of POI cases is not identified, and is believed to be multifactorial. Strategies to POI include hormone replacement and infertility treatment. Assisted conception with donated oocytes has been proven to achieve pregnancy in POI women. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation have been used to preserve ovarian reserve in women undergoing cancer treatments. Primary ovarian insufficiency (POI), commonly referred to as premature ovarian failure (POF), is defined as the occurrence of amenorrhea (for 4 months or more) before the age of 40 in women, accompanied with an increase of serum FSH to menopausal level (usually over 40 IU L 1 , obtained at least 1 month apart), and estradiol levels less than 50 pg mL 1 (which indicate hypoestrogenism) [1]. Primary ovarian insufficiency is first brought to light by Fuller Albright in 1942, who emphasized that the end stage of ovarian function is the primary defect rather than abnormality in gonadotropin secretion [2], and avoided the discomforting and inaccurate stressing on "failure", like death-sentence for ovarian function and conception.Menopause is a destined phase of women, which is expected to occur at around the age of (50±4) years in US women [3]. The age of 40 is two standard deviations below this average [4]. With an incidence of 1% in women under the age of 40, and 0.1% in women under the age of 30 [5], POI renders patients estrogen deficiency and anovulation, resulting in vasomotor symptoms (hot flashes and night sweats), atrophic vaginitis, dyspareunia, primary or secondary amenorrhea, and infertility. 76% of POI cases developed after normal puberty and establishment of regular menses [6]. Some of such conditions occur after stopping...

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“…A X-linked mutation leading to an increased risk for POF is the fragile X premutation [48]. It is characterized by a large CGG repeat track (55-199 repeats) in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene located at Xq27.3.…”

Section: Candidate Genes On the X Chromosomementioning

confidence: 99%

Insight into the Genomics of Premature Ovarian Failure

Stigliani¹

2013

J Mol Genet Med

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Primary Ovarian Failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles. It causes infertility in ~1% of women <40 years of age and it has important health consequences for affected patients. POF is a heterogeneous disease, which can develop as a result of a broad variety of pathogenic mechanisms including genetic, autoimmune and iatrogenic causes. However, the mechanisms that cause ovarian dysfunction are poorly understood. Focus on genetic component of the disease has revealed the existence of several causal genetic defects, thus indicating that in addition to some monogenic forms, POF may frequently be a multifactorial disease involving several gene abnormalities and chromosome aberrations. Moreover, most recent studies have highlighted that epigenetic mechanisms may give an additional contribution to POF pathogenesis. This review gives a picture of the state of the art of the complex genetic and epigenetic defects associated with POF, being it clear that a deep comprehension of the molecular etiology of POF may in future early identify those women with higher risk of POF.

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Examination of reproductive aging milestones among women who carry the FMR1premutation

Abstract: Possible molecular mechanisms to explain the non-linear repeat size risk for ovarian insufficiency are discussed.

Cited by 205 publications

References 44 publications

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

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

An update on primary ovarian insufficiency

Insight into the Genomics of Premature Ovarian Failure

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