Clinical characteristics and genetic analysis in women with premature ovarian insufficiency

Ferrarini, Eleonora; Russo, Laura; Fruzzetti, Franca; Agretti, Patrizia; Marco, Giuseppina De; Dimida, Antonio; Gianetti, Elena; Simoncini, Tommaso; Simi, Paolo; Baldinotti, Fulvia; Benelli, Elena; Pucci, Enrico; Pinchera, Aldo; Vitti, Paolo; Tonacchera, Massimo

doi:10.1016/j.maturitas.2012.09.017

Cited by 26 publications

(14 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several BMP15 gene mutations have been reported in primary ovarian insufficiency (POI) patients with primary or secondary amenorrhea (Takebayashi et al ., 2000; Di Pasquale et al ., 2004, 2006; Chand et al ., 2006; Dixit et al ., 2006; Persani et al ., 2010; Tiotiu et al ., 2010; Auclair et al ., 2013; Ferrarini et al ., 2013). The first missense mutation in the BMP15 gene was identified in two Italian sisters with familial ovarian dysgenesis and primary amenorrhea (Di Pasquale et al ., 2004).…”

Section: Role Of Bmps In Female Reproductive Pathologymentioning

confidence: 99%

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

Chang

Qiao

Leung

2016

Hum. Reprod. Update

222

207

View full text Add to dashboard Cite

BACKGROUNDInitially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation. This review summarizes the current knowledge on the physiological role and molecular determinants of these ovarian regulatory factors within the human germline-somatic regulatory loop.OBJECTIVE AND RATIONALEThe regulation of ovarian function remains poorly characterized in humans because, while the fundamental process of follicular development and oocyte maturation is highly similar across species, most information on the regulation of ovarian function is obtained from studies using rodent models. Thus, this review focuses on the studies that used human biological materials to gain knowledge about human ovarian biology and disorders and to develop strategies for preventing, diagnosing and treating these abnormalities.SEARCH METHODSRelevant English-language publications describing the roles of BMPs or growth differentiation factors (GDFs) in human ovarian biology and phenotypes were comprehensively searched using PubMed and the Google Scholar database. The publications included those published since the initial identification of BMPs in the mammalian ovary in 1999 through July 2016.OUTCOMESStudies using human biological materials have revealed the expression of BMPs, GDFs and their putative receptors as well as their molecular signaling in the fundamental cells (oocyte, cumulus/granulosa cells (GCs) and theca/stroma cells) of the ovarian follicles throughout follicle development. With the availability of recombinant human BMPs/GDFs and the development of immortalized human cell lines, functional studies have demonstrated the physiological role of intra-ovarian BMPs/GDFs in all aspects of ovarian functions, from follicle development to steroidogenesis, cell–cell communication, oocyte maturation, ovulation and luteal function. Furthermore, there is crosstalk between these potent ovarian regulators and the endocrine signaling system. Dysregulation or naturally occurring mutations within the BMP system may lead to several female reproductive diseases. The latest development of recombinant BMPs, synthetic BMP inhibitors, gene therapy and tools for BMP-ligand sequestration has made the BMP pathway a potential therapeutic target in certain human fertility disorders; however, further clinical trials are needed. Recent studies have indicated that GDF8 is an intra-ovarian factor that may play a novel role in regulating ovarian functions in the human ovary.WIDER IMPLICATIONSIntra-ovarian BMPs/GDFs are critical regulators of folliculogenesis and human ovarian functions. Any dysregulation or variations in these ligand...

show abstract

Section: Role Of Bmps In Female Reproductive Pathologymentioning

confidence: 99%

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

Chang

Qiao

Leung

2016

Hum. Reprod. Update

222

207

View full text Add to dashboard Cite

show abstract

“…Table 1 shows the prevalence of FMR1 premutation detected in POF patients from studies performed in different countries. 3,4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] 23 Italy (8%) Murray 24 UK 254 POF (2%) Guo 25 Han Chinese 2/379 POF (0.5%) Bouali et al 26 Tunusia 5/100 POF (5%) Lu et al 7 Han Chinese 1/122 POF (0.8%)…”

Section: Discussionmentioning

confidence: 99%

Evaluation of FMR1 gene mutations in Turkish women newly diagnosed with primary ovarian failure

Sarıkaya

Tokmak

Çakar

et al. 2019

Int J Reprod Contracept Obstet Gynecol

View full text Add to dashboard Cite

Background: One of the known causes of ovarian dysfunction is fragile X mental retardation gene 1 (FMR1) premutation. The prevalence of FMR1 premutation in primary ovarian failure (POF) cases may differ between the studies due to some reasons including POF definition, definition of premutation, and determination of study population, ethnicity, genetic and environmental factors. In this study authors aimed to determine the prevalence of FMR1 mutations in patients who applied to present clinic and diagnosed as POF.Methods: This retrospective cohort study was conducted on 200 women who had been newly diagnosed with POF in present clinic between 2013 and 2014. The presence of cytogenetic fragility was firstly investigated in all patients by using the lymphocyte culture method, and molecular analysis of the FMR1 gene was then performed. Genomic DNA’s of cases were isolated using standard protocols, followed by polymerase chain reaction amplification with an appropriate program. Fragment analysis of the amplification products were performed by agarose gel electrophoresis.Results: Cytogenetic analysis results in 200 cases were numerically and structurally normal in all patients, and as a result of molecular genetic analysis of FMR1 gene; 1 (0.5%) patient had complete mutation and 9 (4.5%) patients had premutation carriage.Conclusions: FMR1 gene mutations are common in women with POF. These mutations should be investigated in all patients presenting with POF, particularly in cases with early onset and family history of POF, and also genetic counseling should be given to those patients.

show abstract

“…As for our patient, the diagnosis of POI was first suspected when a primary amenorrhea was associated with a hypergonadotropic hypogonadism, a normal AFC and a normal AMH. Such situations were formerly investigated with invasive techniques like an ovarian biopsy [13], in the certainty of a negative screening for FMR1 mutation or permutation [14] and a normal karyotype [15], trying to characterize a histological anomaly that could explain the clinical presentation. Of course, the possibility of genetic testing and the potential association of genetic mutation with POI open a new window of opportunity in the diagnosis and the support of these patients [16] [17].…”

Section: Discussionmentioning

confidence: 99%

Fertility Preservation in Premature Ovarian Insufficiency (POI) Secondary to FSH Receptor Gene (FSHR) Mutation: Is There a New Hope?

Pradervand¹,

Antaki²,

Phillips³

et al. 2017

CRCM

View full text Add to dashboard Cite

A 19 years old patient with primary amenorrhea was referred to our center. Based on discrepancy between high follicle stimulating hormone (FSH) level and normal ovarian reserve parameters, follicle stimulating hormone receptor (FSHR) mutation was screened. The patient was homozygous in exon 6 of the FSHR gene for the new variant c.479T > C and predicted to result in an aminoacid substitution p.Ile160Thr. One year later, her anti-müllerian hormone (AMH) level inexplicably decreased. Oocyte vitrification was thus offered for fertility preservation. After 17 days of recombinant follicle stimulating hormone (recFSH) (900 IU daily), no follicular growth was seen and estradiol levels remained low. In vitro maturation (IVM) was then suggested. Ten oocytes were successfully vitrified.

show abstract

Clinical characteristics and genetic analysis in women with premature ovarian insufficiency

Cited by 26 publications

References 41 publications

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

Evaluation of FMR1 gene mutations in Turkish women newly diagnosed with primary ovarian failure

Fertility Preservation in Premature Ovarian Insufficiency (POI) Secondary to FSH Receptor Gene (FSHR) Mutation: Is There a New Hope?

Contact Info

Product

Resources

About