PMID- 15730416
OWN - NLM
STAT- MEDLINE
DCOM- 20050616
LR  - 20061115
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 62
IP  - 3
DP  - 2005 Mar
TI  - Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1.
PG  - 336-42
AB  - OBJECTIVE: To identify MEN1 gene mutations and characterize clinical 
      manifestations in Chinese kindred with multiple endocrine neoplasia type 1 (MEN1) 
      in Taiwan. PATIENTS AND METHODS: Eight unrelated subjects (one male and seven 
      females, age range 26-70 years) with clinical manifestations of MEN1 were 
      analysed. In addition, 45 relatives that included 10 affected (three males and 
      seven females, age range 32-53 years) and 35 unaffected (17 males and 18 females, 
      age range 15-80 years) subjects were evaluated. Genomic DNA extraction, 
      polymerase chain reaction (PCR) and DNA sequence analysis were performed 
      according to standard procedures. RESULTS: We identified heterozygous MEN1 gene 
      mutations in all eight probands and 10 affected subjects as well as in 13 
      clinically asymptomatic relatives. Novel mutations included a missense mutation 
      in a heterozygous mutation in exon 9 (GAC --> CAC) resulting in a substitution of 
      aspartic acid by histidine at codon 418 (family 1); a nonsense mutation at codon 
      556 of exon 10 (GAG --> TAG) resulting in a stop codon and termination (family 
      2); a missense mutation in exon 2 (GGG --> GAG) causing the substitution of 
      glycine by glutamic acid at codon 110 (family 3); and a deletion/insertion 
      mutation in nucleotide 1200 of exon 8 resulting in frameshift and early 
      termination (family 4). Affected subjects in families 5-7 shared the same C 
      insertion at nucleotide 1650 of exon 10, similar to that previously described as 
      a hotspot for mutation, and proband 8 had a previously described mutation in 
      intron 4 of the MEN1 gene (IVS4-9 G --> A). We also found that 18 (58%) of our 31 
      MEN1 mutant carriers had clinical symptoms, whereas four (13%) had biochemical 
      abnormalities without clinical symptoms, and nine (29%) were unaffected both 
      clinically and biochemically. CONCLUSIONS: We have identified four novel 
      mutations in the MEN1 gene in patients with MEN1 in Taiwan.
FAU - Jap, Tjin-Shing
AU  - Jap TS
AD  - Section of Biochemistry, Department of Pathology and Laboratory Medicine, 
      Division of Metabolism and Endocrinology, Taipei Venterans General Hospital, 
      Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. 
      tsjap@vghtpe.gov.tw
FAU - Chiu, Chih-Yang
AU  - Chiu CY
FAU - Won, Justin Ging-Shing
AU  - Won JG
FAU - Wu, Yi-Chi
AU  - Wu YC
FAU - Chen, Harn-Shen
AU  - Chen HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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  - Aged, 80 and over
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Female
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Pedigree
MH  - Proto-Oncogene Proteins/*genetics
MH  - Taiwan
EDAT- 2005/02/26 09:00
MHDA- 2005/06/17 09:00
CRDT- 2005/02/26 09:00
PHST- 2005/02/26 09:00 [pubmed]
PHST- 2005/06/17 09:00 [medline]
PHST- 2005/02/26 09:00 [entrez]
AID - CEN2219 [pii]
AID - 10.1111/j.1365-2265.2005.02219.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2005 Mar;62(3):336-42. doi: 
      10.1111/j.1365-2265.2005.02219.x.