Titre
p.Ala541Thr variant of MEN1 gene: a non deleterious polymorphism or a pathogenic mutation?
Type
article
Institution
Externe
Périodique
Auteur(s)
Nozières, C.
Auteure/Auteur
Zhang, C.X.
Auteure/Auteur
Buffet, A.
Auteure/Auteur
Dupasquier, S.
Auteure/Auteur
Vargas-Poussou, R.
Auteure/Auteur
Guillaud-Bataille, M.
Auteure/Auteur
Cordier-Bussat, M.
Auteure/Auteur
Ruszniewski, P.
Auteure/Auteur
Christin-Maitre, S.
Auteure/Auteur
Murat, A.
Auteure/Auteur
Groussin, L.
Auteure/Auteur
Vezzosi, D.
Auteure/Auteur
Cardot-Bauters, C.
Auteure/Auteur
Hervieu, V.
Auteure/Auteur
Joly, M.O.
Auteure/Auteur
Giraud, S.
Auteure/Auteur
Odou, M.F.
Auteure/Auteur
Gimenez-Roqueplo, A.P.
Auteure/Auteur
Goudet, P.
Auteure/Auteur
Borson-Chazot, F.
Auteure/Auteur
Calender, A.
Auteure/Auteur
Contributrices/contributeurs
Sarfati, E.
Caron, P.
Krivstky, A.
Bertagna, F.
Brunaud, L.
Levy, P.
Peix, J.L.
Rohmer, V.
Delemer, B.
Houllier, P.
de Boisvilliers, F.
Galinat, S.
Wojtusciszyn, A.
Verier-Mine, O.
Reffet, S.
Khiter, C.
Carpentier, B.
Ronci-Chaix, N.
Guignat, L.
Baudry, A.
Nion-Larmurier, I.
Vacher-Lavenu, M.C.
Berger, F.
Costes-Martineau, V.
Delisle, B.
Cezard, J.P.
Parfait, B.
Barlier, A.
Odou, M.F.
Porchet, N.
Cadiot, G.
Bouchard, P.
Brue, T.
Mitry, E.
Vantyghem, M.C.
Couvelard, A.
Danel, C.
Niccoli, P.
Baudin, E.
Tabarin, A.
Chabre, O.
de Boullay, H.
Beckers, A.
Orgiazzi, J.
Ménégaux, F.
Chabrier, G.
Verges, B.
Penfornis, A.
Chanson, P.
Rodier, M.
Archambeaud, F.
Lombard-Bohas, C.
Chayvialle, J.A.
Groupes de travail
Groupe français des tumeurs endocrines (GTE)
Liens vers les personnes
ISSN
2213-3941
Statut éditorial
Publié
Date de publication
2014-07
Volume
75
Numéro
3
Première page
133
Dernière page/numéro d’article
140
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant inherited syndrome, related to mutations in the MEN1 gene. Controversial data suggest that the nonsynonymous p.Ala541Thr variant, usually considered as a non-pathogenic polymorphism, may be associated with an increased risk of MEN1-related lesions in carriers.
The aim of this study was to evaluate the pathogenic influence of the p.Ala541Thr variant on clinical and functional outcomes.
We analysed a series of 55 index patients carrying the p.Ala541Thr variant. Their clinical profile was compared to that of 117 MEN1 patients. The biological impact of the p.Ala541Thr variant on cell growth was additionally investigated on menin-deficient Leydig cell tumour (LCT)10 cells generated from Men1+/Men1- heterozygous knock-out mice, and compared with wild type (WT).
The mean age at first appearance of endocrine lesions was similar in both p.Ala541Thr carriers and MEN1 patients, but no p.Ala541Thr patient had more than one cardinal MEN1 lesion at initial diagnosis. A second MEN1 lesion was diagnosed in 13% of MEN1 patients and in 7% of p.Ala541Thr carriers in the year following preliminary diagnosis. Functional studies on LCT10 cells showed that overexpression of the p.Ala541Thr variant did not inhibit cell growth, which is in direct contrast to results obtained from investigation of WT menin protein.
Taken together, these data raise the question of a potential pathogenicity of the p.Ala541Thr missense variant of menin that commonly occurs within the general population. Additional studies are required to investigate whether it may be involved in a low-penetrance MEN1 phenotype.
The aim of this study was to evaluate the pathogenic influence of the p.Ala541Thr variant on clinical and functional outcomes.
We analysed a series of 55 index patients carrying the p.Ala541Thr variant. Their clinical profile was compared to that of 117 MEN1 patients. The biological impact of the p.Ala541Thr variant on cell growth was additionally investigated on menin-deficient Leydig cell tumour (LCT)10 cells generated from Men1+/Men1- heterozygous knock-out mice, and compared with wild type (WT).
The mean age at first appearance of endocrine lesions was similar in both p.Ala541Thr carriers and MEN1 patients, but no p.Ala541Thr patient had more than one cardinal MEN1 lesion at initial diagnosis. A second MEN1 lesion was diagnosed in 13% of MEN1 patients and in 7% of p.Ala541Thr carriers in the year following preliminary diagnosis. Functional studies on LCT10 cells showed that overexpression of the p.Ala541Thr variant did not inhibit cell growth, which is in direct contrast to results obtained from investigation of WT menin protein.
Taken together, these data raise the question of a potential pathogenicity of the p.Ala541Thr missense variant of menin that commonly occurs within the general population. Additional studies are required to investigate whether it may be involved in a low-penetrance MEN1 phenotype.
Sujets
PID Serval
serval:BIB_BCD734F21E0C
PMID
Date de création
2024-04-15T21:06:36.062Z
Date de création dans IRIS
2025-05-20T21:13:51Z