PMID- 24997771
OWN - NLM
STAT- MEDLINE
DCOM- 20150410
LR  - 20161031
IS  - 2213-3941 (Electronic)
IS  - 0003-4266 (Linking)
VI  - 75
IP  - 3
DP  - 2014 Jul
TI  - p.Ala541Thr variant of MEN1 gene: a non deleterious polymorphism or a pathogenic 
      mutation?
PG  - 133-40
LID - S0003-4266(14)00069-9 [pii]
LID - 10.1016/j.ando.2014.05.003 [doi]
AB  - CONTEXT: 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. OBJECTIVE: The aim of this study was to 
      evaluate the pathogenic influence of the p.Ala541Thr variant on clinical and 
      functional outcomes. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.
CI  - Copyright (c) 2014 Elsevier Masson SAS. All rights reserved.
FAU - Nozieres, Cecile
AU  - Nozieres C
AD  - Federation d'endocrinologie du Pole Lyon-Est, universite Lyon 1, groupement 
      hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron cedex, 
      France; UMR 5201 genetique, signalisation et cancer, centre Leon-Berard, 69008 
      Lyon, France. Electronic address: cnozieres@yahoo.fr.
FAU - Zhang, Chang-Xian
AU  - Zhang CX
AD  - UMR 5201 genetique, signalisation et cancer, centre Leon-Berard, 69008 Lyon, 
      France.
FAU - Buffet, Alexandre
AU  - Buffet A
AD  - Service de genetique, hopital europeen Georges-Pompidou, Assistance 
      publique-Hopitaux de Paris, 75015 Paris, France; Faculte de medecine, universite 
      Paris-Descartes, Sorbonne Paris-Cite, 75006 Paris, France; Inserm, UMR970, Paris 
      cardiovascular research center, 75015 Paris, France.
FAU - Dupasquier, Stephanie
AU  - Dupasquier S
AD  - Laboratoire de genetique moleculaire, hopital Edouard-Herriot, batiment B7, 69347 
      Lyon cedex 03, France.
FAU - Vargas-Poussou, Rosa
AU  - Vargas-Poussou R
AD  - Service de genetique, hopital europeen Georges-Pompidou, Assistance 
      publique-Hopitaux de Paris, 75015 Paris, France; Faculte de medecine, universite 
      Paris-Descartes, Sorbonne Paris-Cite, 75006 Paris, France; Inserm, UMR970, Paris 
      cardiovascular research center, 75015 Paris, France.
FAU - Guillaud-Bataille, Marine
AU  - Guillaud-Bataille M
AD  - Laboratoire d'oncogenetique, hopital Cochin, 75679 Paris cedex 14, France.
FAU - Cordier-Bussat, Martine
AU  - Cordier-Bussat M
AD  - Inserm U 865, universite Claude-Bernard-Lyon 1, 7-11, rue Guillaume-Paradin, 
      69372 Lyon cedex 08, France.
FAU - Ruszniewski, Philippe
AU  - Ruszniewski P
AD  - Service de gastro-enterologie, hopital Beaujon, 100, boulevard du 
      General-Leclerc, 92110 Clichy, France.
FAU - Christin-Maitre, Sophie
AU  - Christin-Maitre S
AD  - Service d'endocrinologie, faculte de medecine, universite Paris VI, hopital 
      Saint-Antoine, Assistance publique-Hopitaux de Paris, 184, rue du Faubourg 
      Saint-Antoine, 75571 Paris cedex 12, France.
FAU - Murat, Arnaud
AU  - Murat A
AD  - Clinique endocrinologie, maladies metaboliques et nutrition, hopital de 
      l'Hotel-Dieu, CHU de Nantes, place Alexis-Ricordeau, BP 100, 44093 Nantes cedex 
      1, France.
FAU - Groussin, Lionel
AU  - Groussin L
AD  - Service d'endocrinologie et maladies metaboliques, faculte de medecine, 
      universite Paris-Descartes, hopital Cochin, Assistance publique-Hopitaux de 
      Paris, 75679 Paris cedex 14, France.
FAU - Vezzosi, Delphine
AU  - Vezzosi D
AD  - Service d'endocrinologie, maladies metaboliques et nutrition, hopital Larrey, 
      31059 Toulouse cedex, France.
FAU - Cardot-Bauters, Catherine
AU  - Cardot-Bauters C
AD  - Clinique Marc-Linquette, 59037 Lille, France.
FAU - Hervieu, Valerie
AU  - Hervieu V
AD  - Service d'anatomo-pathologie, hopital Edouard-Herriot, place d'Arsonval, 69003 
      Lyon, France.
FAU - Joly, Marie-Odile
AU  - Joly MO
AD  - Service d'anatomo-pathologie, hopital Edouard-Herriot, place d'Arsonval, 69003 
      Lyon, France.
FAU - Giraud, Sophie
AU  - Giraud S
AD  - UMR 5201 genetique, signalisation et cancer, centre Leon-Berard, 69008 Lyon, 
      France.
FAU - Odou, Marie-Francoise
AU  - Odou MF
AD  - Service de genetique moleculaire, pole de pathologie biologie, Eurasante, CHRU de 
      Lille, 59000 Lille, France.
FAU - Gimenez-Roqueplo, Anne-Paule
AU  - Gimenez-Roqueplo AP
AD  - Service de genetique, hopital europeen Georges-Pompidou, Assistance 
      publique-Hopitaux de Paris, 75015 Paris, France; Faculte de medecine, universite 
      Paris-Descartes, Sorbonne Paris-Cite, 75006 Paris, France; Inserm, UMR970, Paris 
      cardiovascular research center, 75015 Paris, France.
FAU - Goudet, Pierre
AU  - Goudet P
AD  - Service de chirurgie endocrinienne, hopital du Bocage, 2, boulevard de 
      Lattre-de-Tassigny, 21034 Dijon, France.
FAU - Borson-Chazot, Francoise
AU  - Borson-Chazot F
AD  - Federation d'endocrinologie du Pole Lyon-Est, universite Lyon 1, groupement 
      hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron cedex, 
      France.
FAU - Calender, Alain
AU  - Calender A
AD  - UMR 5201 genetique, signalisation et cancer, centre Leon-Berard, 69008 Lyon, 
      France; Laboratoire de genetique moleculaire, hopital Edouard-Herriot, batiment 
      B7, 69347 Lyon cedex 03, France. Electronic address: alain.calender@chu-lyon.fr.
CN  - Groupe francais des tumeurs endocrines (GTE)
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140702
PL  - France
TA  - Ann Endocrinol (Paris)
JT  - Annales d'endocrinologie
JID - 0116744
RN  - 0 (MEN1 protein, human)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adenoma/genetics
MH  - Adult
MH  - Animals
MH  - Cell Line, Tumor
MH  - Female
MH  - Heterozygote
MH  - Humans
MH  - Hyperparathyroidism/genetics
MH  - Leydig Cell Tumor/genetics
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - *Mutation
MH  - Phenotype
MH  - Pituitary Neoplasms/genetics
MH  - Polymorphism, Genetic/*genetics
MH  - Proto-Oncogene Proteins/deficiency/*genetics
MH  - Transfection
OTO - NOTNLM
OT  - Multiple endocrine neoplasia type 1
OT  - Mutation
OT  - Neoplasie endocrinienne multiple de type 1
OT  - Penetrance
OT  - Polymorphism
OT  - Polymorphisme
OT  - Predisposition
OT  - Predisposition
OT  - Penetrance
FIR - Sarfati, E
IR  - Sarfati E
FIR - Caron, P
IR  - Caron P
FIR - Krivstky, A
IR  - Krivstky A
FIR - Bertagna, F
IR  - Bertagna F
FIR - Brunaud, L
IR  - Brunaud L
FIR - Levy, P
IR  - Levy P
FIR - Peix, J L
IR  - Peix JL
FIR - Rohmer, V
IR  - Rohmer V
FIR - Delemer, B
IR  - Delemer B
FIR - Houllier, P
IR  - Houllier P
FIR - de Boisvilliers, F
IR  - de Boisvilliers F
FIR - Galinat, S
IR  - Galinat S
FIR - Wojtusciszyn, A
IR  - Wojtusciszyn A
FIR - Verier-Mine, O
IR  - Verier-Mine O
FIR - Reffet, S
IR  - Reffet S
FIR - Khiter, C
IR  - Khiter C
FIR - Carpentier, B
IR  - Carpentier B
FIR - Ronci-Chaix, N
IR  - Ronci-Chaix N
FIR - Guignat, L
IR  - Guignat L
FIR - Baudry, A
IR  - Baudry A
FIR - Nion-Larmurier, I
IR  - Nion-Larmurier I
FIR - Vacher-Lavenu, M-C
IR  - Vacher-Lavenu MC
FIR - Berger, F
IR  - Berger F
FIR - Costes-Martineau, V
IR  - Costes-Martineau V
FIR - Delisle, B
IR  - Delisle B
FIR - Cezard, J-P
IR  - Cezard JP
FIR - Parfait, B
IR  - Parfait B
FIR - Barlier, A
IR  - Barlier A
FIR - Odou, M-F
IR  - Odou MF
FIR - Porchet, N
IR  - Porchet N
FIR - Cadiot, G
IR  - Cadiot G
FIR - Bouchard, P
IR  - Bouchard P
FIR - Brue, T
IR  - Brue T
FIR - Mitry, E
IR  - Mitry E
FIR - Vantyghem, M-C
IR  - Vantyghem MC
FIR - Couvelard, A
IR  - Couvelard A
FIR - Danel, C
IR  - Danel C
FIR - Niccoli, P
IR  - Niccoli P
FIR - Baudin, E
IR  - Baudin E
FIR - Tabarin, A
IR  - Tabarin A
FIR - Chabre, O
IR  - Chabre O
FIR - de Boullay, H
IR  - de Boullay H
FIR - Beckers, A
IR  - Beckers A
FIR - Orgiazzi, J
IR  - Orgiazzi J
FIR - Menegaux, F
IR  - Menegaux F
FIR - Chabrier, G
IR  - Chabrier G
FIR - Verges, B
IR  - Verges B
FIR - Penfornis, A
IR  - Penfornis A
FIR - Chanson, P
IR  - Chanson P
FIR - Rodier, M
IR  - Rodier M
FIR - Archambeaud, F
IR  - Archambeaud F
FIR - Lombard-Bohas, C
IR  - Lombard-Bohas C
FIR - Chayvialle, J-A
IR  - Chayvialle JA
EDAT- 2014/07/07 06:00
MHDA- 2015/04/11 06:00
CRDT- 2014/07/07 06:00
PHST- 2014/02/03 00:00 [received]
PHST- 2014/04/23 00:00 [revised]
PHST- 2014/05/12 00:00 [accepted]
PHST- 2014/07/07 06:00 [entrez]
PHST- 2014/07/07 06:00 [pubmed]
PHST- 2015/04/11 06:00 [medline]
AID - S0003-4266(14)00069-9 [pii]
AID - 10.1016/j.ando.2014.05.003 [doi]
PST - ppublish
SO  - Ann Endocrinol (Paris). 2014 Jul;75(3):133-40. doi: 10.1016/j.ando.2014.05.003. 
      Epub 2014 Jul 2.