Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations

Fonseca, Dora Janeth; Patiño, Liliana Catherine; Suárez, Yohjana Carolina; Rodríguez, Asid de Jesús; Mateus, Heidi; Jiménez, Karen M.; Ortega‐Recalde, Oscar; Díaz-Yamal, Ivonne; Laissue, Paul

doi:10.1016/j.fertnstert.2015.04.016

Cited by 66 publications

(52 citation statements)

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“…The use of next generation sequencing (NGS) technology during last few years has led to the discovery of new POI causative sequence variants, mainly in monogenic familial presentations of the disease (Laissue, ). At least three studies using different NGS formats have addressed unrelated cases of POI (Bouilly et al., ; Fonseca et al., ; Patiño et al., ; Tucker et al., ). Recently, we have analyzed 69 unrelated POI women via whole exome sequencing (WES) and identified 55 mutations (in 49 genes) underlying possible functional effects (Patiño et al., ).…”

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“…Our findings showed that the p.Ser1804Leu, p.Ala2316Val, and p.Pro2359Ala mutations led to decreased NOTCH2 transcriptional activity (14% to 27% reduction; Figure ). The differences between the WT and mutant forms were moderate, which was understandable as POI etiology may result from the epistatic interaction of numerous genes carrying different variants having moderate/severe functional effects (Bouilly et al., ; Fonseca et al., ; Patiño et al., ; Laissue, ). In addition, we consider the idea that these variants represent POI genetic predisposition factors cannot be ruled out.…”

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Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency etiology

et al. 2018

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Primary ovarian insufficiency (POI) is a frequently occurring disease affecting women under 40 years old. Recently, we have analyzed unrelated POI women via whole exome sequencing (WES) and identified NOTCH2 mutations underlying possible functional effects. The present study involved reanalyzing of WES assays. We used in the KGN granulosa-like cell model, a synthetic gene reporter construct driving luciferase gene expression to assess the functional effects of five NOTCH2 mutations identified in POI patients. We found that NOTCH2-p.Ser1804Leu, p.Ala2316Val, and p.Pro2359Ala mutations had a functional impact on the protein's transcrip-

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Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency etiology

et al. 2018

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“…35,36 ADAMTS19 is a member of ADAMTS (a disintegrin-like and metalloprotease with thrombospondin type 1 motif) family of metalloproteinase. Although its role in folliculogenesis or sex steroid regulation has not yet been demonstrated, many publications found an association with POI 37,38 and have shown an interaction with IGF2R 39 and ACVR2B 31 genes.…”

Section: Autosomal Genes and Folliculogenesismentioning

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Primary ovarian insufficiency associated with autosomal abnormalities: from chromosome to genome-wide and beyond

Vichinsartvichai

2016

Menopause

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“…A very recent TSM study of 70 candidate genes has identified potential novel genes (ADAMTS19 and BMPR2) and mutations related to the disease pathogenesis (Fonseca et al, 2015).…”

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Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing

Laissue

2015

Molecular and Cellular Endocrinology

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Premature ovarian failure (POF) is a frequent pathology affecting 1-1.5% of women under 40 years old. Despite advances in diagnosing and treating human infertility, POF is still classified as being idiopathic in 50-80% of cases, strongly suggesting a genetic origin for the disease. Different types of autosomal and X-linked genetic anomalies can originate the phenotype in syndromic and non-syndromic POF cases. Particular interest has been focused on research into non-syndromic POF causative coding variants during the past two decades. This has been based on the assumption that amino acid substitutions might modify the intrinsic physicochemical properties of functional proteins, thereby inducing pathological phenotypes. In this case, a restricted number of mutations might originate the disease. However, like other complex pathologies, POF might result from synergistic/compensatory effects caused by several low-to-mildly drastic mutations which have frequently been classified as non-functional SNPs. Indeed, reproductive phenotypes can be considered as quantitative traits resulting from the subtle interaction of many genes. Although numerous sequencing projects have involved candidate genes, only a few coding mutations explaining a low percentage of cases have been described. Such apparent failure to identify aetiological coding sequence variations might have been due to the inherent molecular complexity of mammalian reproduction and to the difficulty of simultaneously analysing large genomic regions by Sanger sequencing. The purpose of this review is to present the molecular and cellular effects caused by non-synonymous mutations which have been formally associated, by functional tests, with the aetiology of hypergonadotropic non-syndromic POF. Considerations have also been included regarding the polygenic nature of reproduction and POF, as well as future approaches for identifying novel aetiological genes based on next generation sequencing (NGS).

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Next generation sequencing in women affected by nonsyndromic premature ovarian failure displays new potential causative genes and mutations

Cited by 66 publications

References 68 publications

Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency etiology

Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency etiology

Primary ovarian insufficiency associated with autosomal abnormalities: from chromosome to genome-wide and beyond

Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing

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