Journal ArticleDOI
Exome sequencing reveals SYCE1 mutation associated with autosomal recessive primary ovarian insufficiency.
Liat de Vries,Liat de Vries,Doron M. Behar,Doron M. Behar,Pola Smirin-Yosef,Irina Lagovsky,Shay Tzur,Lina Basel-Vanagaite,Lina Basel-Vanagaite +8 more
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TLDR
It is suggested that the nonsense mutation identified accounts for the POI phenotype, highlighting the importance of the synaptonemal complex and meiosis in ovarian function.Abstract:
Context: Primary ovarian insufficiency (POI) is caused by ovarian follicle depletion or follicle dysfunction. The phenotypic spectrum ranges from absence of pubertal maturation to early menopause. Genes involved in essential steps in chromosome synapsis and recombination during meiosis, such as synaptonemal complex central element 1 (SYCE1), have been shown to cause POI in animal models. We describe for the first time a homozygous mutation in SYCE1 in humans. Objective: To identify the genetic cause of POI in an Israeli Arab family with a consanguineous pedigree. Setting and Design: A family-based genetic study conducted at a tertiary medical center. Patients: Two daughters of consanguineous parents (first cousins) from a 13-member family were diagnosed with POI. Genotyping was performed in the index patients, their parents, and four unaffected siblings. Intervention: DNA from the affected sisters was subjected to whole-exome sequencing. The genotypes of interest were confirmed and genotypes of the additi...read more
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Journal ArticleDOI
Genetics of primary ovarian insufficiency: new developments and opportunities
TL;DR: Given the slow progress in candidate-gene analysis and relatively small sample sizes available for GWAS, family-based whole exome and whole genome sequencing appear to be the most promising approaches for detecting potential genes responsible for POI.
Journal ArticleDOI
MCM9 Mutations Are Associated with Ovarian Failure, Short Stature, and Chromosomal Instability
Michelle A. Wood-Trageser,Fatih Gurbuz,Svetlana A. Yatsenko,Elizabeth P. Jeffries,L. Damla Kotan,Urvashi Surti,Deborah M. Ketterer,Jelena Matic,Jacqueline Chipkin,Huaiyang Jiang,Michael A. Trakselis,A. Kemal Topaloglu,Aleksandar Rajkovic +12 more
TL;DR: Autosomal-recessive variants in MCM9 cause a genomic-instability syndrome associated with hypergonadotropic hypogonadism and short stature, and preferential sensitivity of germline meiosis to MCM 9 functional deficiency and compromised DNA repair in the somatic component most likely account for the ovarian failure and short size.
Journal ArticleDOI
Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic Spectrum.
Elena J. Tucker,Elena J. Tucker,Sonia Grover,Sonia Grover,Anne Bachelot,Anne Bachelot,Philippe Touraine,Philippe Touraine,Andrew H. Sinclair,Andrew H. Sinclair +9 more
TL;DR: Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.
Journal ArticleDOI
Genetics of primary ovarian insufficiency
TL;DR: The principal X‐linked and autosomal genes involved in syndromic and non‐syndromic forms of POI are reviewed 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.
Journal ArticleDOI
Molecular Genetics of Premature Ovarian Insufficiency
TL;DR: The research into miRNA and age at menopause represents an emerging field that will help unveil the molecular mechanisms underlying pathogenesis of POI and shed light on the genetic architecture is important in interpreting pathogenesis and will facilitate risk prediction for POI.
References
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Univariate Discrete Distributions
TL;DR: In this paper, the authors propose a family of Discrete Distributions, which includes Hypergeometric, Mixture, and Stopped-Sum Distributions (see Section 2.1).
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Univariate Discrete Distributions.
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Primary Ovarian Insufficiency
TL;DR: A 30-year-old woman presents with a history of no menses since she stopped taking oral contraceptives 6 months ago in order to conceive, and the prolactin level is normal, the follicle-stimulating hormone (FSH) level is in the menopausal range.
Journal ArticleDOI
Primary ovarian insufficiency
TL;DR: The main symptom is absence of regular menstrual cycles, and the diagnosis is confirmed by detection of raised follicle-stimulating hormone and declined oestradiol concentrations in the serum, suggesting a primary ovarian defect.
Journal ArticleDOI
Premature ovarian failure: a systematic review on therapeutic interventions to restore ovarian function and achieve pregnancy
YM van Kasteren,J. Schoemaker +1 more
TL;DR: The collected data of observational, uncontrolled and controlled studies indicate that POF patients still have a 5-10% chance to conceive following diagnosis, and there is no evidence that any treatment can enhance this pregnancy rate.