Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN1).
Dideoxyfingerprinting was used to screen for germline and somatic MEN1 mutations. This method, applied to a panel of germline DNA from 15 probands with multiple endocrine neoplasia type 1 (MEN-1), allowed confident discovery of the MEN1 gene. Germline MEN1 mutation has been found in 47 out of 50 probands with familial MEN-1, in 7 out of 8 cases with sporadic MEN-1, and in 1 out of 3 cases with atypical sporadic MEN-1. Germline MEN1 mutation was not found in any of five probands with familial hyperparathyroidism. Somatic MEN1 mutations were found in 7 out of 33 parathyroid tumours not associated with MEN-1. Allowing for repeating mutations, a total of 47 different germline or somatic MEN1 mutations have been identified. Most predict inactivation of the encoded 'menin' protein. supporting expectations that MEN1 is a tumour suppressor gene. The 16 observed missense mutations were distributed across the gene, suggesting that many domains are important to its as yet unknown functions.
Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892-1802, USA. StephenM@ambintra.niddk.nih.gov
S J
SJ
Marx
S K
SK
Agarwal
M B
MB
Kester
C
C
Heppner
Y S
YS
Kim
M R
MR
Emmert-Buck
L V
LV
Debelenko
I A
IA
Lubensky
Z
Z
Zhuang
S C
SC
Guru
P
P
Manickam
S E
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Olufemi
M C
MC
Skarulis
J L
JL
Doppman
R H
RH
Alexander
L A
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Liotta
F S
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Collins
S C
SC
Chandrasekharappa
A M
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Spiegel
A L
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Burns
D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000235:genetics
D003062:Codon; D004273:DNA, Neoplasm