Elevated prevalence of 35-44 FMR1 trinucleotide repeats in women with diminished ovarian reserve

Pastore, Lisa M.; Young, S.L.; Baker, Valerie L.; Karns, Logan B.; Williams, Christopher D.; Silverman, Lawrence M.

doi:10.1016/j.fertnstert.2011.07.354

Cited by 6 publications

(11 citation statements)

References 13 publications

(20 reference statements)

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“…Participant characteristics were compared by 1-way analysis of variance (ANOVA) across race–ethnic groups for continuous variables and by χ 2 tests for categorical variables. Discrete categories for CGG repeat length were selected a priori to respond to prior reports of high normal 4,5 and low normal 7 repeats potentially being associated with early ovarian aging. The categorical distributions of CGG repeat lengths were compared across race–ethnic groups using a Fisher exact test with α = .05.…”

Section: Methodsmentioning

confidence: 99%

“…Women with premutation level repeats in this gene (55-199 CGG) are at increased risk of premature ovarian failure, [1][2][3] alternatively termed primary ovarian insufficiency. Some reports have suggested that women with 35 to 44 CGGs, 4,5 35 to 54 CGGs, 6 and <28 CGG repeat lengths 7 may be associated with less severe ovarian dysfunction, often manifest as diminished ovarian reserve. These findings are less consistent, as reviewed by Pastore and Johnson.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

et al. 2016

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, and potentially women with high normal (35)(36)(37)(38)(39)(40)(41)(42)(43)(44) or low normal (<28) CGG repeats, are at risk of premature ovarian aging. The scarcity of population data on CGG repeats <45 CGG, and variation in raceethnicity, makes it difficult to determine true associations. DNA was analyzed for FMR1 CGG repeat lengths from 803 women (386 caucasians, 219 African Americans, 102 Japanese, and 96 Chinese) from the US-based Study of Women's Health Across the Nation (SWAN). Participants had 1 menses in the 3 months before enrollment, 1 pregnancy, no history of infertility or hormonal therapy, and menopause 46 years. Statistical analyses used Fisher exact tests. Among these women with normal reproductive histories, significant FMR1 repeat length differences were found across race-ethnicity for both the longer (P ¼ .0002) and the shorter (P < .0001) alleles. The trinucleotide length variance was greater for non-Asian than Asian women (P < .0001), despite identical median values. Our data indicate that short allele lengths <25 CGG on one or both alleles are more common in non-Asian than Asian women. We confirm the minor allele in the 35 to 39 CGG range among Asians as reported previously. Only 2 (0.3%) premutation carriers were identified. These data demonstrate that FMR1 distributions do vary by race-ethnicity, even within the ''normal'' range. This study indicates the need to control for race-ethnicity in FMR1 ovarian aging research and provides race-ethnic population data for females separated by allele.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

et al. 2016

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“…Six studies, representing 975 patients and 1749 controls, were eligible for evaluation of the premutation and intermediate alleles in DOR [15,[18][19][20]30,33]. The prevalence of premutation varied from 1.3 to 15.95% among cases and from 0.0 to 0.6% among controls, while the prevalence of intermediate varied from 1.6 to 13.3% among DOR, and from Notes: NA: data not available; -: data didn't mention in the studies; a: small sample size didn't include in meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

Association between the FMR1 CGG repeat lengths and the severity of idiopathic primary ovarian insufficiency: a meta analysis

Huang

Zhang

Liu³

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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2019) Association between the FMR1 CGG repeat lengths and the severity of idiopathic primary ovarian insufficiency: a meta analysis, Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 3116-3122, ABSTRACT Aim: Reports on the association of the CGG repeat length in the FMR1 gene with the severity of idiopathic POI are inconclusive. Therefore, a meta analysis was performed to investigate the relationship between the expansion of repeat CGG and idiopathic POI risk. Methods: Up to January 2019, 18 case-control or cohort studies involving 3022 idiopathic POI patients and 8461 controls were included for meta analysis. Results: Thirteen studies, including 2047 cases and 6912 controls, met our criteria for the assessment of the premutation and intermediate repeat length in patients patients with POI. Compared with controls, FMR1 gene premutation is significantly associated with POI (OR ¼ 8.13; 95% CI: 4.35-15.19; p < .00001), whereas there was no significant correlation between intermediate repeat length and POI (OR ¼ 0.86; 95% CI: 0.62-1.18; p ¼ .34). Six studies, representing 975 patients and 1749 controls, were eligible for evaluation of the premutation and intermediate repeat length in diminished ovarian reserve (DOR). The association between premutation and DOR was significant (OR¼14.87; 95% CI:5.20-42.52; p < 0.00001), while no significant correlation of intermediate size to DOR was found in the case-control comparison (OR ¼ 0.98; 95% CI: 0.65-1.47; p ¼ 0.93). Conclusion: There is a close association between premutation of the FMR1 gene and increased susceptibility to idiopathic POI of each stage and no correlation between intermediate repeat length of the FMR1 gene and the severity of idiopathic POI. ARTICLE HISTORY KEYWORDSIdiopathic primary ovarian insufficiency; diminished ovarian reserve, fragile X mental retardation 1 (FMR1); CGG repeat length; meta analysis CONTACT Hong Jiang

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“…The criteria for exclusion were: known cause of elevated FSH for one's age unrelated to fragile X (e.g., surgical removal of either one or both ovaries, chemotherapy or radiation therapy, Turners Syndrome, autoimmune disease), or a family history of FXS or premutation. Knowing that FSH values can vary by assay (Scriver et al 2010;Taieb et al 2002), deidentified samples were run at each satellite site and the primary site (University of Virginia), and adjusted accordingly to ensure consistency in the enrollment criteria across sites as described previously (Pastore et al 2012;Scriver et al 2010).…”

Section: Participantsmentioning

confidence: 99%

“…If the mother has approximately 100 CGG repeats in the FMR1 gene, there is a nearly 100 % chance that her child(ren) will have the full mutation (Nolin et al 2003(Nolin et al , 2011, although this risk is moderated when the FMR1 CGG repeat is interspersed with one or more AGG's (Nolin et al 2013). Research since the 1990's has provided evidence that women with a premutation allele (Karimov et al 2011;Sherman 2000), and potentially women with a high normal (Pastore et al 2012;Streuli et al 2009) or gray zone (Gleicher et al 2009;Karimov et al 2011) level repeat (35-44 and 45-54 CGG repeats, respectively), have an increased risk of primary ovarian insufficiency (specifically, a diagnosis of premature ovarian failure and/or DOR). Thus, there is reproductive relevance to women from being tested for the FMR1 premutation.…”

Section: Introductionmentioning

confidence: 99%

Attitudes Towards Potentially Carrying the FMR1 Premutation: Before vs After Testing of Non‐Carrier Females with Diminished Ovarian Reserve

Pastore

Antero

Ventura

et al. 2014

Journal of Genetic Counseling

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Diminished ovarian reserve (DOR) and premature ovarian failure are associated with elevated FMR1 CGG repeat alleles. We assessed pretest attitudes about potentially carrying the FMR1 premutation (FXP) (>55 CGG repeats) among reproductive age women compared with attitudes after learning their non-carrier status. Ninety-two women with DOR, regular menses and no family history of Fragile X Syndrome underwent FMR1 testing and completed attitudinal questionnaires before (T1) and 3 months after learning the test results (T2). The analysis utilized signed rank tests and α=0.05. Very few women thought they were likely to have a FXP (6.6%). More participants thought FMR1 premutations were “serious” at T2 (62.9%) than at T1 (46.1%, p<0.0003). When asked at T1 to “describe your feelings when you consider that you are potentially a carrier” of a FXP, 10% had negative feelings, 50% felt ambivalent, and 40% had positive feelings. At T2, feelings about not being a carrier were significantly more favorable (p<0.0001): negative (0%), ambivalent (6.5%), positive (93%). Corroborating prior reports, few women had a negative view of FXP, perhaps anticipating that carrying the FXP explains their infertility. Perception of the seriousness of FXP increased after learning they did not carry the FXP, which would be predicted by health belief models.

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Elevated prevalence of 35-44 FMR1 trinucleotide repeats in women with diminished ovarian reserve

Cited by 6 publications

References 13 publications

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

FMRI CGG Repeats:Reference Levels and Race-Ethnic Variation in Women With Normal Fertility (Study of Women’s Health Across the Nation)

Association between the FMR1 CGG repeat lengths and the severity of idiopathic primary ovarian insufficiency: a meta analysis

Attitudes Towards Potentially Carrying the FMR1 Premutation: Before vs After Testing of Non‐Carrier Females with Diminished Ovarian Reserve

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