Article (Scientific journals)
Higher risk of death among MEN1 patients with mutations in the JunD interacting domain. A Groupe d'étude des Tumeurs Endocrines (GTE) cohort study
Thevenon, Julien; Bourredjem, Abderrahmane; Faivre, Laurence et al.
2013In Human Molecular Genetics
Peer Reviewed verified by ORBi
 

Files


Full Text
HumMolGene-Thevenon2013.pdf
Publisher postprint (193.27 kB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] BackgroundMultiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities.MethodsWe report on a cohort of MEN1 patients from the Groupe d'etude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totalling 262 families and 806 patients were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families.ResultsAccounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR=1.88: 95%-CI=1.15- 3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR=2.34; 95%-CI=1.23- 4.43).ConclusionThis genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Thevenon, Julien
Bourredjem, Abderrahmane
Faivre, Laurence
Cardot-Bauters, Catherine
Calender, Alain
Murat, Arnaud
Giraud, Sophie
Niccoli, Patricia
Odou, Marie-Francoise
Borson-Chazot, Francoise
Barlier, Anne
Lombard-Bohas, Catherine
Clauser, Eric
Tabarin, Antoine
Parfait, Beatrice
Chabre, Olivier
CASTERMANS, Emilie ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
BECKERS, Albert ;  Centre Hospitalier Universitaire de Liège - CHU > Endocrinologie clinique
Ruszniewski, Philippe
Le Bras, Morgane
Delemer, Brigitte
Bouchard, Philippe
Guilhem, Isabelle
Rohmer, Vincent
Goichot, Bernard
Caron, Philippe
Baudin, Eric
Chanson, Philippe
Groussin, Lionel
Du Boullay, Hélène
Weryha, Georges
Lecomte, Pierre
Penfornis, Alfred
Bihan, Hélène
Archambeaud, Françoise
Kerlan, Véronique
Duron, Françoise
Kuhn, Jean-Marc
Verges, Bruno
Rodier, Michel
Renard, Michel
Sadoul, Jean-Louis
Binquet, Christine
Goudet, Pierre
More authors (34 more) Less
Language :
English
Title :
Higher risk of death among MEN1 patients with mutations in the JunD interacting domain. A Groupe d'étude des Tumeurs Endocrines (GTE) cohort study
Publication date :
2013
Journal title :
Human Molecular Genetics
ISSN :
0964-6906
eISSN :
1460-2083
Publisher :
Oxford University Press, Oxford, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 29 March 2013

Statistics


Number of views
252 (16 by ULiège)
Number of downloads
245 (6 by ULiège)

Scopus citations®
 
73
Scopus citations®
without self-citations
52
OpenCitations
 
70

Bibliography


Similar publications



Contact ORBi