Anti-Mullerian hormone indicates early ovarian decline in fragile X mental retardation (FMR1) premutation carriers: a preliminary study

Rohr, J.; Allen, Emily G.; Charen, Krista; Giles, James R.; He, Weiya; Dominguez, Celia E.; Sherman, Stephanie L.

doi:10.1093/humrep/den050

Cited by 81 publications

(61 citation statements)

References 35 publications

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“…More recent studies have shown reduced levels of AMH among premutation carriers compared with non-carriers, again, consistent with an aging ovary (121).…”

Section: Non-syndromic Poimentioning

confidence: 64%

Genetics of primary ovarian insufficiency

et al. 2016

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Primary ovarian insufficiency (POI) is characterized by a loss of ovarian function before the age of 40 and account for one major cause of female infertility. POI relevance is continuously growing because of the increasing number of women desiring conception beyond 30 years of age, when POI prevalence is >1%. POI is highly heterogeneous and can present with ovarian dysgenesis and primary amenorrhea, or with secondary amenorrhea, and it can be associated with other congenital or acquired abnormalities. In most cases POI remains classified as idiopathic. However, the age of menopause is an inheritable trait and POI has a strong genetic component. This is confirmed by the existence of several candidate genes, experimental and natural models. The variable expressivity of POI defect may indicate that, this disease may frequently be considered as a multifactorial or oligogenic defect. The most common genetic contributors to POI are the X chromosome‐linked defects. Here, we review the principal X‐linked and autosomal genes involved in syndromic and non‐syndromic forms of POI with the expectation that this list will soon be upgraded, thus allowing the possibility to predict the risk of an early age at menopause in families with POI.

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“…More recent studies have shown reduced levels of AMH among premutation carriers compared with non-carriers, again, consistent with an aging ovary (121).…”

Section: Non-syndromic Poimentioning

confidence: 64%

Genetics of primary ovarian insufficiency

et al. 2016

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“…Although some studies showed evidence of earlier age of onset of FXPOI and higher penetrance of mid-range premutations of 80 -100 repeats, 24,25 we chose to use the definition of higher risk alleles of Ն70 repeats in our calculation as defined by Rohr et al 22 We choose to use Ն70 repeats in our calculations for FXTAS and FXPOI for consistency in defining larger premutation alleles and because several studies examined penetrance of larger premutation alleles in FXTAS and FXPOI. 16,17,22 …”

Section: Discussionmentioning

confidence: 99%

“…Female premutation carriers show overall higher levels of follicular stimulating hormone than do normal or full mutation carriers, along with decreased levels of anti-Müllerian hormone, Inhibin A, and Inhibin B-all indicators of ovarian decline. 19,21,22 All women who are premutation carriers will have an increased risk of suffering from FXPOI, 22,23 with evidence of earlier onset of FXPOI in female carriers of mid premutations range of 80 -100 repeats than carriers of shorter or longer premutation alleles. 24,25 Penetrance of FXPOI seems to be higher in carriers of mid premutation alleles (18.6%), when compared with lower or longer premutation carriers, 5.9% and 12.5%, respectively.…”

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confidence: 99%

FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: Insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United States

Hantash

Goos

Crossley

et al. 2011

Genetics in Medicine

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Purpose: Fragile X syndrome is caused by expansion and methylation of a CGG tract in the 5Ј untranslated region of the FMR1 gene. The estimated frequency of expanded alleles (Ն55 repeats) in the United States is 1:257-1:382, but these estimates were not calculated from unbiased populations. We sought to determine the frequency of fragile X syndrome premutation (55-200 repeats) and full mutation (Ͼ200 repeats) alleles in nonselected, unbiased populations undergoing routine carrier screening for other diseases. Methods: A previously validated laboratory-developed test using triplet-primed polymerase chain reaction was used to detect premutation and full mutation alleles in an unselected series of 11,759 consecutive cystic fibrosis carrier screening samples and 2011 samples submitted for screening for genetic diseases prevalent among the Ashkenazi Jewish population. Results: Premutations were identified in 48 cystic fibrosis screening samples (1:245) and 15 samples (1:134) from the Ashkenazi Jewish population. Adjusted for the ethnic mix of the US population and self-reported ethnicity in our screening population, the estimated female premutation carrier frequency in the United States was 1:178. The calculated frequency of full mutation alleles was 1:3335 overall, and the calculated premutation frequency in males was 1:400. Based on frequency of larger, Ն70 repeat alleles, and reported penetrance, the calculated fragile X-associated tremor and ataxia syndrome, and fragile X-associated primary ovarian insufficiency frequencies is 1:4848 and 1:3560, respectively. Conclusion: Our calculated fragile X syndrome carrier rate is higher than previous estimates for the US population and warrants further consideration of population-based carrier screening. Genet Med 2011:13(1): 39 -45.

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“…Notwithstanding the extensive number of scientific papers in the last few years, no definitive consensus exists on the characterization of altered ovarian function [29]. A combination of hormonal markers like serum follicle-stimulating hormone (FSH) [52], serum AMH [79] and the antral follicle count [77] may help in diagnosing early decline in ovarian follicular activity. The antral follicle count remains perhaps the best predictor of the ovarian response to the controlled ovarian stimulation after the AMH assay itself [80,88] Although early follicular phase serum FSH levels are a well established marker of ovarian reserve [18], the correlation may be poor compared to other markers.…”

Section: Cgg Mutations and Biomarkers Of Ovarian Reservementioning

confidence: 99%

The impact of FMR1 gene mutations on human reproduction and development: a systematic review

Noto

Harrity

Walsh

et al. 2016

J Assist Reprod Genet

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Purpose This is a comprehensive review of the literature in this field attempting to put the FMR1 gene and its evaluation into context, both in general and for the reproductive health audience. Methods Online database search of publications with systematic review of all papers relevant to ovarian reserve and assisted reproduction was done. Results Relevant papers were identified and assessed, and an attempt was made to understand, rationalize and explain the divergent views in this field of study. Seminal and original illustrations were employed. Conclusions FMR1 is a highly conserved gene whose interpretation and effect on outcomes remains controversial in the reproductive health setting. Recent re-evaluations of the commonly accepted normal range have yielded interesting tools for possibly explaining unexpected outcomes in assisted reproduction. Fragile X investigations should perhaps become more routinely assessed in the reproductive health setting, particularly following a failed treatment cycle where oocyte quality is thought to be a contributing factor, or in the presence of a surprise finding of diminished ovarian reserve in a young patient.

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Anti-Mullerian hormone indicates early ovarian decline in fragile X mental retardation (FMR1) premutation carriers: a preliminary study

Abstract: These preliminary data suggest that AMH levels indicate early ovarian decline among women with longer FMR1 repeat alleles; moreover, AMH appears to be a better marker than FSH in identifying this early decline.

Cited by 81 publications

References 35 publications

Genetics of primary ovarian insufficiency

Genetics of primary ovarian insufficiency

FMR1 premutation carrier frequency in patients undergoing routine population-based carrier screening: Insights into the prevalence of fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency in the United States

The impact of FMR1 gene mutations on human reproduction and development: a systematic review

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