Title :

Msh2 c. 1022t>c, p. Leu341pro is a founder pathogenic variation and a major cause of lynch syndrome in the north of france

Author(s) :

Vermaut, Catherine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Leclerc, Julie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Vasseur, Francis [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Wacrenier, Agnes [Auteur]
Institut de Pathologie [CHU Lille]
Lovecchio, Tonio [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Boidin, Denis [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Rebergue, Marie-Helene [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Cattan, Stephane [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Manouvrier, Sylvie [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Lejeune, Sophie [Auteur]
Service de Génétique Médicale [Lille]
Buisine, Marie-Pierre [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172

Journal title :

Genes, Chromosomes & Cancer

Abbreviated title :

Genes Chromosomes Cancer

Volume number :

59

Pages :

111-118

Publisher :

Wiley

Publication date :

2019-08-21

ISSN :

1098-2264

Keyword(s) :

Lynch syndrome
founder pathogenic variant
MSH2
missense variant
hereditary cancer

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Interpretation of missense variants remains a major challenge for genetic diagnosis, even in well-known genes such as the DNA-mismatch repair (MMR) genes involved in Lynch syndrome. We report the characterization of a ...
Show more >Interpretation of missense variants remains a major challenge for genetic diagnosis, even in well-known genes such as the DNA-mismatch repair (MMR) genes involved in Lynch syndrome. We report the characterization of a variant in MSH2: c.1022T>C, which was identified in 20 apparently unrelated families living in the North of France. A total of 150 patients from 20 families were included in this study. Family segregation studies, tumor analyses and functional analyses at both the RNA and protein levels were performed. Founder effect was evaluated by haplotype analysis.We show that MSH2 c.1022T>C is a missense variant (p.Leu341Pro) that affects protein stability. This variant is frequent in the North of France (7.7% of pathogenic variations identified in MMR genes), and is located on an ancestral haplotype. It is associated with a high risk of a broad tumor spectrum including brain and cutaneous cancers. The MSH2 c.1022T>C variant is a pathogenic founder variation associated with a high risk of cancer. These findings have important implications for genetic counseling and management of variant carriers.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Université de Lille

Collections :

• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
• Miniaturisation pour la Synthèse, l'Analyse et la Protéomique (MSAP) - USR 3290

Submission date :

2021-09-02T07:02:09Z
2024-03-29T07:23:33Z