Homozygous hypomorphic

BRCA2 exome cancer Fanconi anemia meiosis primary ovarian insufficiency

Journal

Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R

Informations de publication

Date de publication:
01 Jun 2020
Historique:
received: 05 11 2019
revised: 08 04 2020
accepted: 12 04 2020
entrez: 3 6 2020
pubmed: 3 6 2020
medline: 3 6 2020
Statut: aheadofprint

Résumé

Primary ovarian insufficiency (POI) affects 1% of women under 40 years and is a public health problem. The genetic causes of POI are highly heterogeneous with isolated or syndromic forms. Recently, variants in genes involved in DNA repair have been shown to cause POI. Notably, syndromic POI with Fanconi anaemia (FA) traits related to biallelic Exome sequencing (ES) was performed in the patient. We also performed functional studies, including a homologous recombination (HR) test, cell proliferation, radiation-induced RAD51 foci formation assays and chromosome breakage studies in primary and lymphoblastoid immortalised cells. The expression of ES identified a homozygous missense c.8524C>T/p.R2842C We describe the functional assessment of a homozygous hypomorphic

Sections du résumé

BACKGROUND BACKGROUND
Primary ovarian insufficiency (POI) affects 1% of women under 40 years and is a public health problem. The genetic causes of POI are highly heterogeneous with isolated or syndromic forms. Recently, variants in genes involved in DNA repair have been shown to cause POI. Notably, syndromic POI with Fanconi anaemia (FA) traits related to biallelic
METHODS METHODS
Exome sequencing (ES) was performed in the patient. We also performed functional studies, including a homologous recombination (HR) test, cell proliferation, radiation-induced RAD51 foci formation assays and chromosome breakage studies in primary and lymphoblastoid immortalised cells. The expression of
RESULTS RESULTS
ES identified a homozygous missense c.8524C>T/p.R2842C
CONCLUSION CONCLUSIONS
We describe the functional assessment of a homozygous hypomorphic

Identifiants

pubmed: 32482800
pii: jmedgenet-2019-106672
doi: 10.1136/jmedgenet-2019-106672
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Sandrine Caburet (S)

Institut Jacques Monod, Université de Paris, Paris, Île-de-France, France.

Abdelkader Heddar (A)

Faculte de Medecine, Universite Paris Saclay, Hopital Bicêtre APHP, Le Kremlin-Bicetre, France.

Elodie Dardillac (E)

Institut Cochin, INSERM U1016, UMR 8104 CNRS, Université de Paris, Paris, Île-de-France, France.

Héléne Creux (H)

Service de Gynécologie et Médecine de la Reproduction, CHU de Bordeaux, Bordeaux, Aquitaine, France.

Marie Lambert (M)

Service de Gynécologie et Médecine de la Reproduction, CHU de Bordeaux, Bordeaux, Aquitaine, France.

Sébastien Messiaen (S)

UMR Stabilité Génétique, Cellules Souches et Radiations, Université Paris-Saclay, Fontenay aux Roses, Île-de-France, France.

Sophie Tourpin (S)

UMR Stabilité Génétique, Cellules Souches et Radiations, Université Paris-Saclay, Fontenay aux Roses, Île-de-France, France.

Gabriel Livera (G)

UMR Stabilité Génétique, Cellules Souches et Radiations, Université Paris-Saclay, Fontenay aux Roses, Île-de-France, France.

Bernard S Lopez (BS)

Institut Cochin, INSERM U1016, UMR 8104 CNRS, Université de Paris, Paris, Île-de-France, France micheline.misrahi@aphp.fr bernard.lopez@inserm.fr.

Micheline Misrahi (M)

Faculte de Medecine, Universite Paris Saclay, Hopital Bicêtre APHP, Le Kremlin-Bicetre, France micheline.misrahi@aphp.fr bernard.lopez@inserm.fr.

Classifications MeSH