PMID- 17854391
OWN - NLM
STAT- MEDLINE
DCOM- 20090730
LR  - 20220408
IS  - 1365-2265 (Electronic)
IS  - 0300-0664 (Linking)
VI  - 68
IP  - 3
DP  - 2008 Mar
TI  - Analysis of gross deletions in the MEN1 gene in patients with multiple endocrine 
      neoplasia type 1.
PG  - 350-4
AB  - BACKGROUND: Mutation analysis with direct DNA sequencing is commonly used for the 
      molecular diagnosis of multiple endocrine neoplasia type 1 (MEN1). However, a 
      significant number of patients, despite clinical features of MEN1, do not show 
      MEN1 mutations on direct DNA sequencing. Some of these patients may have gross 
      gene deletions not detected by direct DNA sequencing or mutations in the 
      noncoding regions of the gene not examined routinely. OBJECTIVE: To determine the 
      prevalence of gross deletions in MEN1 in a large cohort of MEN1 patients. 
      PATIENTS AND METHODS: During 1997-2006, we screened MEN1 mutations by direct DNA 
      sequencing in 368 probands referred to our diagnostic molecular genetic 
      laboratory. Of these, 101 probands (23 familial, 78 sporadic) fulfilled the 
      clinical criteria for MEN1 (presence of at least two of the parathyroid, 
      pancreatic or pituitary tumours) but were negative for mutations on DNA 
      sequencing. Their DNA samples were examined for gross deletions of one or more 
      exons of MEN1 by using multiple ligation-dependent probe amplification (MLPA) and 
      long-range polymerase chain reaction (PCR) amplification. We also sequenced the 
      minimal promoter region of MEN1 for mutations in the familial cases. RESULTS: We 
      identified a gross deletion involving exons 5 and 6 of MEN1 in one proband 
      (prevalence rate 1%). The sequencing of the minimal promoter region in the 
      familial cases revealed no mutations. CONCLUSION: Gross deletion in the MEN1 gene 
      is an uncommon cause of MEN1 and should be tested for in patients with a high 
      clinical suspicion but without mutations on direct DNA sequencing.
FAU - Owens, Martina
AU  - Owens M
AD  - Department of Molecular Genetics, Royal Devon and Exeter Hospital, Peninsula 
      Medical School, Exeter, UK.
FAU - Ellard, Sian
AU  - Ellard S
FAU - Vaidya, Bijay
AU  - Vaidya B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070914
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Exons
MH  - Female
MH  - *Gene Deletion
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*genetics
MH  - Young Adult
EDAT- 2007/09/15 09:00
MHDA- 2009/07/31 09:00
CRDT- 2007/09/15 09:00
PHST- 2007/09/15 09:00 [pubmed]
PHST- 2009/07/31 09:00 [medline]
PHST- 2007/09/15 09:00 [entrez]
AID - CEN3045 [pii]
AID - 10.1111/j.1365-2265.2007.03045.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2008 Mar;68(3):350-4. doi: 
      10.1111/j.1365-2265.2007.03045.x. Epub 2007 Sep 14.