PMID- 12049533
OWN - NLM
STAT- MEDLINE
DCOM- 20020712
LR  - 20220310
IS  - 0004-0010 (Print)
IS  - 0004-0010 (Linking)
VI  - 137
IP  - 6
DP  - 2002 Jun
TI  - Genotype-phenotype analysis in multiple endocrine neoplasia type 1.
PG  - 641-7
AB  - HYPOTHESIS: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is an autosomal 
      dominant disorder caused by germline mutations in the MEN1 gene and characterized 
      by multiple endocrine tumors, most notably in the parathyroid glands, pituitary, 
      and pancreas. The syndrome demonstrates variable expressivity and considerable 
      genetic heterogeneity. Patient data were examined for possible associations 
      between genotype and phenotype. DESIGN: We reviewed recorded medical data from 
      1975 to 2001 on patients with MEN 1 and compared specific types and locations of 
      MEN1 gene mutations with manifestations of the syndrome. PATIENTS AND RESULTS: We 
      identified 109 affected patients from 24 MEN 1 kindreds. The phenotypic 
      expression of MEN 1 in affected individuals included hyperparathyroidism in 74%, 
      pancreatic endocrine tumors in 51%, and pituitary tumors in 35%. Twelve of 14 
      insulinomas occurred in patients with pituitary tumors. Mutation analysis was 
      completed in 14 of 24 kindreds (80 of the 109 patients). Mutations were most 
      common in exons 2 (31%), 9 (15%), and 10 (23%). All 21 patients with frameshift 
      mutations (and known pancreatic endocrine tumor status) had such tumors. 
      Pituitary tumors were associated with frameshift mutations in exon 2. 
      CONCLUSIONS: The type and location of MEN1 mutations may be associated with the 
      phenotypic expression of specific tumors. Such information may assist in the 
      genetic counseling and surveillance of at-risk patients. A specific 
      genotype-phenotype correlation is unlikely because of the heterogeneity of the 
      mutations in the MEN1 gene.
FAU - Kouvaraki, Maria A
AU  - Kouvaraki MA
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer 
      Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
FAU - Lee, Jeffrey E
AU  - Lee JE
FAU - Shapiro, Suzanne E
AU  - Shapiro SE
FAU - Gagel, Robert F
AU  - Gagel RF
FAU - Sherman, Steven I
AU  - Sherman SI
FAU - Sellin, Rena V
AU  - Sellin RV
FAU - Cote, Gilbert J
AU  - Cote GJ
FAU - Evans, Douglas B
AU  - Evans DB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Surg
JT  - Archives of surgery (Chicago, Ill. : 1960)
JID - 9716528
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Female
MH  - Frameshift Mutation
MH  - Genotype
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Insulinoma/*genetics
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Neoplasm Proteins/*genetics
MH  - Pancreatic Neoplasms/*genetics
MH  - Phenotype
MH  - Pituitary Neoplasms/*genetics
MH  - *Proto-Oncogene Proteins
MH  - Retrospective Studies
EDAT- 2002/06/07 10:00
MHDA- 2002/07/13 10:01
CRDT- 2002/06/07 10:00
PHST- 2002/06/07 10:00 [pubmed]
PHST- 2002/07/13 10:01 [medline]
PHST- 2002/06/07 10:00 [entrez]
AID - sws1002 [pii]
AID - 10.1001/archsurg.137.6.641 [doi]
PST - ppublish
SO  - Arch Surg. 2002 Jun;137(6):641-7. doi: 10.1001/archsurg.137.6.641.