Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency aetiology

Liliana C Patiño, Isabelle Beau, Adrien Morel, Brigitte Delemer, Jacques Young, Nadine Binart, Paul Laissue

Research output: Contribution to journalArticle

4 Scopus citations


Primary ovarian insufficiency (POI) is a frequently occurring disease affecting women under 40 years old. Recently, we have analysed unrelated POI women via whole-exome sequencing (WES) and identified NOTCH2 mutations underlying possible functional effects. The present study involved reanalysing 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 transcriptional activity. The results have demonstrated for the first time that NOTCH2 mutations contribute to POI aetiology. We therefore recommend sequencing NOTCH2's open reading frame in large panels of POI patients to establish an accurate genotype-phenotype correlation. We cannot rule out the fact that patients affected by Alagille syndrome carrying NOTCH2 mutations may suffer ovarian dysfunction. This article is protected by copyright. All rights reserved.

Translated title of the contributionEvidencia funcional que implica mutaciones de NOTCH2 con la etiología molecular de la POI
Original languageEnglish (US)
Article number3
Pages (from-to)1
Number of pages10
JournalHuman Mutation
Issue number10
StatePublished - Oct 10 2018

Fingerprint Dive into the research topics of 'Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency aetiology'. Together they form a unique fingerprint.

  • Cite this