PMID- 15670192
OWN - NLM
STAT- MEDLINE
DCOM- 20050420
LR  - 20220408
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 62
IP  - 2
DP  - 2005 Feb
TI  - Detection of an MEN1 gene mutation depends on clinical features and supports 
      current referral criteria for diagnostic molecular genetic testing.
PG  - 169-75
AB  - OBJECTIVE: Diagnostic molecular genetic testing for multiple endocrine neoplasia 
      type 1 (MEN1) has been available since the identification of the MEN1 gene in 
      1997. Mutation screening of the MEN1 gene has been recommended for patients who 
      meet clinical criteria for MEN1 (at least two of the following: parathyroid 
      hyperplasia, pancreatic endocrine tumour or pituitary adenoma) and those in whom 
      a diagnosis of MEN1 is suspected. We examined the appropriateness of these 
      clinical criteria. PATIENTS AND METHODS: A total of 292 patients were referred 
      for diagnostic testing. The coding region of the MEN1 gene was sequenced in 186 
      index cases and mutation testing was requested for 106 subjects, including 83 
      asymptomatic relatives. RESULTS: MEN1 gene mutations were identified in 68/186 
      index cases (37%). Twenty-nine of the 60 MEN1 mutations reported are novel. The 
      likelihood of finding a mutation was correlated with the number of MEN1-related 
      tumours (mutation detection rate of 79%, 37% and 15% in patients with three, two 
      and one main MEN1-related tumours; P < or = 0.00001) and increased in the 
      presence of a family history (mutation detection rate of 91%, 69% and 29%vs. 69%, 
      23% and 0% in sporadic cases with three, two or one main MEN1-related tumours, 
      respectively; P < or = 0.00001). The pick-up rate in the 83% of subjects who met 
      proposed criteria for diagnostic testing was 42%, but in those who did not meet 
      these criteria this fell to 0%. CONCLUSIONS: The likelihood of finding an MEN1 
      mutation depends on the clinical features of the patient and their family. This 
      large series supports present referral criteria for diagnostic mutation 
      screening, but suggests that patients with sporadic isolated tumours rarely have 
      MEN1 mutations.
FAU - Ellard, S
AU  - Ellard S
AD  - Department of Molecular Genetics, Royal Devon & Exeter NHS Foundation Trust, 
      Exeter, UK. s.ellard@exeter.ac.uk
FAU - Hattersley, A T
AU  - Hattersley AT
FAU - Brewer, C M
AU  - Brewer CM
FAU - Vaidya, B
AU  - Vaidya B
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  - Child
MH  - DNA Mutational Analysis
MH  - Exons
MH  - Female
MH  - *Genetic Testing
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - *Patient Selection
MH  - Phenotype
MH  - Predictive Value of Tests
MH  - Proto-Oncogene Proteins/*genetics
MH  - Referral and Consultation
MH  - Statistics, Nonparametric
EDAT- 2005/01/27 09:00
MHDA- 2005/04/21 09:00
CRDT- 2005/01/27 09:00
PHST- 2005/01/27 09:00 [pubmed]
PHST- 2005/04/21 09:00 [medline]
PHST- 2005/01/27 09:00 [entrez]
AID - CEN2190 [pii]
AID - 10.1111/j.1365-2265.2005.02190.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2005 Feb;62(2):169-75. doi: 
      10.1111/j.1365-2265.2005.02190.x.