PMID- 12112656
OWN - NLM
STAT- MEDLINE
DCOM- 20020805
LR  - 20071115
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 20
IP  - 1
DP  - 2002 Jul
TI  - Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search 
      for correlation between phenotype and the functional domains of the MEN1 protein.
PG  - 35-47
AB  - Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disease 
      characterized by endocrine tumors of the parathyroids, the pancreatic islets, and 
      the anterior pituitary. The MEN1 gene encodes menin, a nuclear protein 
      interacting with JunD/AP1, Smad3, NFkappaB, and other proteins involved in 
      transcription and cell growth regulation. Here, by exhaustive sequence analysis 
      of 170 probands/families collected through a French clinical network, we 
      identified 165 mutations located in coding parts of the MEN1 gene, which 
      represent 114 distinct MEN1 germline alterations. These mutations have been 
      included in a MEN1-locus specific database available on the world wide web 
      together with approximately 240 germline and somatic MEN1 mutations listed from 
      international published data. Our mutation series included 56 frameshifts, 23 
      nonsense, 27 missense, and eight deletion or insertion in-frame mutations. 
      Mutations were spread over the entire coding sequence. Taken together, most 
      missense and in-frame MEN1 genomic alterations affect one or all domains of menin 
      interacting with JunD [codons 1-40; 139-242; 323-428], Smad3 [distal to codon 
      478], and NFkappaB [codons 276-479], three major effectors in transcription and 
      cell growth regulation. No correlation has been observed between genotype and 
      MEN1 phenotype. We suggest that the knowledge of structure and location of a 
      specific mutation has not been useful in clinical practice for the follow-up of 
      affected patients and asymptomatic gene carriers. Our results provide the largest 
      series of MEN1 mutations published to date. They will be a useful tool for 
      further studies focusing on the functional effects of missense mutations and 
      understanding which mechanisms or pathways related to multiple menin interactions 
      might be involved in tumorigenesis of endocrine cells.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Wautot, Virginie
AU  - Wautot V
AD  - Laboratoire de Genetique et Cancer, UMR CNRS, Lyon, France.
FAU - Vercherat, Cecile
AU  - Vercherat C
FAU - Lespinasse, James
AU  - Lespinasse J
FAU - Chambe, Beatrice
AU  - Chambe B
FAU - Lenoir, Gilbert M
AU  - Lenoir GM
FAU - Zhang, Chang X
AU  - Zhang CX
FAU - Porchet, Nicole
AU  - Porchet N
FAU - Cordier, Martine
AU  - Cordier M
FAU - Beroud, Christophe
AU  - Beroud C
FAU - Calender, Alain
AU  - Calender A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (DNA, Neoplasm)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Binding Sites/genetics
MH  - DNA Mutational Analysis
MH  - DNA, Neoplasm/chemistry/genetics
MH  - Databases as Topic
MH  - Family Health
MH  - Genotype
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Neoplasm Proteins/*genetics
MH  - Phenotype
MH  - *Proto-Oncogene Proteins
EDAT- 2002/07/12 10:00
MHDA- 2002/08/06 10:01
CRDT- 2002/07/12 10:00
PHST- 2002/07/12 10:00 [pubmed]
PHST- 2002/08/06 10:01 [medline]
PHST- 2002/07/12 10:00 [entrez]
AID - 10.1002/humu.10092 [doi]
PST - ppublish
SO  - Hum Mutat. 2002 Jul;20(1):35-47. doi: 10.1002/humu.10092.