Msh2 c. 1022t>c, p. Leu341pro is a founder ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
PMID :
URL permanente :
Titre :
Msh2 c. 1022t>c, p. Leu341pro is a founder pathogenic variation and a major cause of lynch syndrome in the north of france
Auteur(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
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
Titre de la revue :
Genes, Chromosomes & Cancer
Nom court de la revue :
Genes Chromosomes Cancer
Numéro :
59
Pagination :
111-118
Éditeur :
Wiley
Date de publication :
2019-08-21
ISSN :
1098-2264
Mot(s)-clé(s) :
Lynch syndrome
founder pathogenic variant
MSH2
missense variant
hereditary cancer
founder pathogenic variant
MSH2
missense variant
hereditary cancer
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [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 ...
Lire la suite >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.Lire moins >
Lire la suite >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.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
CNRS
Université de Lille
CNRS
Université de Lille
Collections :
Date de dépôt :
2021-09-02T07:02:09Z
2024-03-29T07:23:33Z
2024-03-29T07:23:33Z