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

Resultado de la investigación: Contribución a RevistaArtículo

1 Cita (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Número de artículo3
Páginas (desde-hasta)1
Número de páginas10
PublicaciónHuman Mutation
Volumen10
N.º10
DOI
EstadoPublished - oct 10 2018
Publicado de forma externa

Citar esto

Patiño, L. C., Beau, I., Morel, A., Delemer, B., Young, J., Binart, N., & Laissue, P. (2018). Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency aetiology. Human Mutation, 10(10), 1. [3]. https://doi.org/10.1002/humu.23667
Patiño, Liliana C ; Beau, Isabelle ; Morel, Adrien ; Delemer, Brigitte ; Young, Jacques ; Binart, Nadine ; Laissue, Paul. / Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency aetiology. En: Human Mutation. 2018 ; Vol. 10, N.º 10. pp. 1.
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abstract = "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.",
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Patiño, LC, Beau, I, Morel, A, Delemer, B, Young, J, Binart, N & Laissue, P 2018, 'Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency aetiology', Human Mutation, vol. 10, n.º 10, 3, pp. 1. https://doi.org/10.1002/humu.23667

Functional evidence implicating NOTCH2 missense mutations in primary ovarian insufficiency aetiology. / Patiño, Liliana C; Beau, Isabelle; Morel, Adrien; Delemer, Brigitte; Young, Jacques; Binart, Nadine; Laissue, Paul.

En: Human Mutation, Vol. 10, N.º 10, 3, 10.10.2018, p. 1.

Resultado de la investigación: Contribución a RevistaArtículo

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AU - Beau, Isabelle

AU - Morel, Adrien

AU - Delemer, Brigitte

AU - Young, Jacques

AU - Binart, Nadine

AU - Laissue, Paul

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/10/10

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N2 - 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.

AB - 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.

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