PMID- 17623761
OWN - NLM
STAT- MEDLINE
DCOM- 20071101
LR  - 20220408
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 92
IP  - 9
DP  - 2007 Sep
TI  - Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 
      unrelated cases.
PG  - 3389-95
AB  - CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is a tumor syndrome of the 
      parathyroid, endocrine pancreas, and anterior pituitary caused by mutations in 
      the MEN1 gene on 11q13. OBJECTIVE: The goal of this study was to determine the 
      MEN1 mutation spectrum and detection rate among Swedish patients and identify 
      which patient categories should be tested for MEN1 mutations. 
      DESIGN/SETTING/PATIENTS: DNA sequences and referral forms from patients referred 
      to the Department of Clinical Genetics at Karolinska University Hospital, Sweden, 
      for clinical MEN1 mutation screening were analyzed. The mutation status of 371 
      patients (including 200 probands) was ascertained, and the multiplex 
      ligation-dependent probe amplification (MLPA) assay was evaluated for the 
      detection of large deletions. MAIN OUTCOME MEASURE: The main outcome measure was 
      MEN1 genotypes. RESULTS: Forty-eight of 200 index cases (24%) shared 40 different 
      mutations (18 novel). A total of 69% of all mutations resulted in a truncated 
      protein. Two large deletions were detected by MLPA. A total of 94% of all MEN1 
      families had a mutation in the coding region of the MEN1 gene. A total of 6% of 
      sporadic cases had MEN1 mutations. There was no correlation between severe 
      disease and mutation type or location. CONCLUSIONS: A total of 4% of all 
      mutations were large deletions, and MLPA is now included in our standard MEN1 
      mutation screening. Individuals with at least one typical endocrine tumour and at 
      least one of the following: 1) a first-degree relative with a major endocrine 
      tumor; 2) an age of onset less than 30 yr; and/or 3) multiple pancreatic 
      tumors/parathyroid hyperplasia were most likely to harbor a mutation; thus these 
      patients should be screened for MEN1 mutations.
FAU - Tham, Emma
AU  - Tham E
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 
      Stockholm, Sweden. emma.tham@karolinska.se
FAU - Grandell, Ulla
AU  - Grandell U
FAU - Lindgren, Eva
AU  - Lindgren E
FAU - Toss, Goran
AU  - Toss G
FAU - Skogseid, Britt
AU  - Skogseid B
FAU - Nordenskjold, Magnus
AU  - Nordenskjold M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070710
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
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  - Female
MH  - Genetic Testing
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation
MH  - Pancreatic Neoplasms/genetics
MH  - Parathyroid Neoplasms/genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Sweden
EDAT- 2007/07/12 09:00
MHDA- 2007/11/02 09:00
CRDT- 2007/07/12 09:00
PHST- 2007/07/12 09:00 [pubmed]
PHST- 2007/11/02 09:00 [medline]
PHST- 2007/07/12 09:00 [entrez]
AID - jc.2007-0476 [pii]
AID - 10.1210/jc.2007-0476 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2007 Sep;92(9):3389-95. doi: 10.1210/jc.2007-0476. Epub 
      2007 Jul 10.