PMID- 17555499
OWN - NLM
STAT- MEDLINE
DCOM- 20111027
LR  - 20070824
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 67
IP  - 3
DP  - 2007 Sep
TI  - Novel MEN1 germline mutations in Brazilian families with multiple endocrine 
      neoplasia type 1.
PG  - 377-84
AB  - OBJECTIVE: To characterize clinical features and identify MEN1 germline mutations 
      in Brazilian families with multiple endocrine neoplasia type 1 (MEN1). Settings 
      Non-profit academic centre. PATIENTS: Fourteen Brazilian families with MEN1 and 
      141 at-risk relatives. RESULTS: We identified 12 different MEN1 disease-causing 
      mutations, seven of them previously unreported: 308delC; 375del21; 549A>T 
      (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families 
      with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by 
      mitochondrial-DNA and Y-chromosome haplotype analyses. Most of the MEN1 single 
      point mutations involved evolutionarily conserved residues, whereas most of the 
      deletion/frameshift changes occurred in GC-rich repetitive regions. Genetic 
      screening of 141 at-risk family members identified 38 MEN1 mutation carriers, 37 
      (97.4%) of whom had at least one major MEN1-related tumour upon clinical 
      investigation. CONCLUSIONS: High frequencies of MEN1 gene mutations were detected 
      in Brazilian families with MEN1, including seven new genetic mutations that are 
      predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data 
      underscore the need to implement a systematic MEN1 screening programme in Brazil.
FAU - Toledo, Rodrigo A
AU  - Toledo RA
AD  - Unidade de Endocrinologia Genetica LIM-25, Endocrinologia, Hospital das Clinicas 
      da Faculdade de Medicina da Universidade de Sao Paulo, Brazil.
FAU - Lourenco, Delmar M Jr
AU  - Lourenco DM Jr
FAU - Coutinho, Flavia L
AU  - Coutinho FL
FAU - Quedas, Elisangela
AU  - Quedas E
FAU - Mackowiack, Ivone
AU  - Mackowiack I
FAU - Machado, Marcel C C
AU  - Machado MC
FAU - Montenegro, Fabio
AU  - Montenegro F
FAU - Cunha-Neto, Malebranche B C
AU  - Cunha-Neto MB
FAU - Liberman, Bernardo
AU  - Liberman B
FAU - Pereira, Maria A A
AU  - Pereira MA
FAU - Correa, Pedro H S
AU  - Correa PH
FAU - Toledo, Sergio P A
AU  - Toledo SP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070606
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Amino Acid Substitution/genetics
MH  - Brazil/epidemiology
MH  - Family
MH  - Family Health
MH  - Female
MH  - Genetic Testing
MH  - *Germ-Line Mutation
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*epidemiology/*genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Risk Factors
MH  - Young Adult
EDAT- 2007/06/09 09:00
MHDA- 2011/10/28 06:00
CRDT- 2007/06/09 09:00
PHST- 2007/06/09 09:00 [pubmed]
PHST- 2011/10/28 06:00 [medline]
PHST- 2007/06/09 09:00 [entrez]
AID - CEN2895 [pii]
AID - 10.1111/j.1365-2265.2007.02895.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2007 Sep;67(3):377-84. doi: 
      10.1111/j.1365-2265.2007.02895.x. Epub 2007 Jun 6.