Exome Sequencing Reveals SYCE1 Mutation Associated With Autosomal Recessive Primary Ovarian Insufficiency

Vries, Liat de; Behar, Doron M.; Smirin‐Yosef, Pola; Lagovsky, Irina; Tzur, Shay; Basel‐Vanagaite, Lina

doi:10.1210/jc.2014-1268

Cited by 149 publications

(117 citation statements)

References 22 publications

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“…The analysis of a few cohorts of 46,XX POI patients by means of high throughput techniques, such as comparative genomic hybridization array (array-CGH) and SNP array, has led to the identification of CNVs affecting several X-linked and autosomal loci with a possible role in female fertility (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). Similarly, the recent application of whole-exome sequencing (WES) to a few POI multigenerational familial cases has succeeded in revealing rare single nucleotide variants affecting genes implicated in ovarian function (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). As already reported in other complex diseases characterized by a great genetic heterogeneity, it is likely that patients with POI may harbor multiple genetic variants.…”

Section: The Heterogeneous Manifestations and Multifactorial Origin Omentioning

confidence: 99%

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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Section: The Heterogeneous Manifestations and Multifactorial Origin Omentioning

confidence: 99%

Genetics of primary ovarian insufficiency

et al. 2016

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“…XX disorders of sexual development (XX-DSD) are infrequent (1), and (46-XX) females with isolated hypergonadotropic ovarian dysgenesis (MIM #233300) constitute a rare, genetically heterogeneous condition. In recent years, XX-DSD with ovarian dysgenesis have been shown to be caused by autosomal recessive mutations in the genes encoding the follicle-stimulating hormone (FSH) receptor, WNT4 (2, 3), R-spondin (4,5), PSMC3IP (6), MCM9 (7), MCM8 (8,9), STAG3 (10), and SYCE1 (11) or by X-linked recessive mutations in BMP15 (12,13). These and other studies indicate that ovarian development is an active process involving signaling pathways and crosstalk between somatic and germ cells and not simply a passive process unfolding in the absence of SRY, the testis determining gene on the Y chromosome (14).…”

Section: Introductionmentioning

confidence: 99%

A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis

Weinberg‐Shukron¹,

Renbaum²,

Kalifa³

et al. 2015

Journal of Clinical Investigation

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“…2 b) [de Vries et al, 2014]. As mentioned above, the SYCE1 C-terminal helix would be involved in its recruitment to the SC by SYCE3 [Lu et al, 2014].…”

Section: Mutations In Genes Coding For Cr Proteinsmentioning

confidence: 90%

“…In the first case, 2 daughters from first cousin parents of Israeli-Arab origin presented POF. Homozygosity mapping followed by exome sequencing and subsequent genotyping in all family members by Sanger sequencing revealed a nonsense homozygous mutation in the SYCE1 gene (613C>T) in both affected sisters [de Vries et al, 2014]. In the second case, the affected patients were 2 azoospermic brothers of Iranian-Jewish origin, whose parents were also first cousins.…”

Section: Mutations In Genes Coding For Cr Proteinsmentioning

confidence: 92%

“…The anomalies were mutations in SYCE1 , reported in siblings born to consanguineous parents of 2 Middle Eastern families [de Vries et al, 2014;Maor-Sagie et al, 2015]. In both families, the parents were heterozygous for the mutation while the patients presented homozygous mutations ( Table 1 ), indicating a recessive inheritance [de Vries et al, 2014;Maor-Sagie et al, 2015].…”

Section: Mutations In Genes Coding For Cr Proteinsmentioning

confidence: 96%

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Mutations in Genes Coding for Synaptonemal Complex Proteins and Their Impact on Human Fertility

Geisinger

Benavente²

2016

Cytogenet Genome Res

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Human infertility is often classified as idiopathic in both males and females. Meiotic errors may account for at least part of these cases. As the synaptonemal complex (SC, a meiosis-specific protein scaffold) is essential for successful meiosis progression, in this paper, we analyzed the mutations in genes coding for SC components described in infertile patients to assess to what extent alterations in the SC can be related to human infertility. So far, mutations in SYCP3 and SYCE1 genes have been reported. While most SYCP3 mutations are heterozygous mutations with dominant-negative effect on the region encoding the C-terminal coiled coil of the protein, SYCE1 mutations are homozygous, which is consistent with a recessive inheritance. Similarities and differences between males and females as well as between mice and humans have been found and are discussed herein. The results suggest that a low percentage of human infertility cases may be explained by mutations in genes coding for SC components. The characterization of these mutations, together with available information from the study of knockout mice, will enable a deeper understanding of the underlying molecular bases for some of the cases of idiopathic infertility.

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Exome Sequencing Reveals SYCE1 Mutation Associated With Autosomal Recessive Primary Ovarian Insufficiency

Abstract: Given the known function of the SYCE1 gene, we suggest that the nonsense mutation identified accounts for the POI phenotype. These results highlight the importance of the synaptonemal complex and meiosis in ovarian function.

Cited by 149 publications

References 22 publications

Genetics of primary ovarian insufficiency

Genetics of primary ovarian insufficiency

A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis

Mutations in Genes Coding for Synaptonemal Complex Proteins and Their Impact on Human Fertility

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