PMID- 9463336
OWN - NLM
STAT- MEDLINE
DCOM- 19980406
LR  - 20220408
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 62
IP  - 2
DP  - 1998 Feb
TI  - Characterization of mutations in patients with multiple endocrine neoplasia type 
      1.
PG  - 232-44
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      characterized by tumors of the parathyroids, pancreatic islets, and anterior 
      pituitary. The MEN1 gene, on chromosome 11q13, has recently been cloned, and 
      mutations have been identified. We have characterized such MEN1 mutations, 
      assessed the reliability of SSCP analysis for the detection of these mutations, 
      and estimated the age-related penetrance for MEN1. Sixty-three unrelated MEN1 
      kindreds (195 affected and 396 unaffected members) were investigated for 
      mutations in the 2,790-bp coding region and splice sites, by SSCP and DNA 
      sequence analysis. We identified 47 mutations (12 nonsense mutations, 21 
      deletions, 7 insertions, 1 donor splice-site mutation, and 6 missense mutations), 
      that were scattered throughout the coding region, together with six polymorphisms 
      that had heterozygosity frequencies of 2%-44%. More than 10% of the mutations 
      arose de novo, and four mutation hot spots accounted for >25% of the mutations. 
      SSCP was found to be a sensitive and specific mutational screening method that 
      detected >85% of the mutations. Two hundred and one MEN1 mutant-gene carriers 
      (155 affected and 46 unaffected) were identified, and these helped to define the 
      age-related penetrance of MEN1 as 7%, 52%, 87%, 98%, 99%, and 100% at 10, 20, 30, 
      40, 50, and 60 years of age, respectively. These results provide the basis for a 
      molecular-genetic screening approach that will supplement the clinical evaluation 
      and genetic counseling of members of MEN1 families.
FAU - Bassett, J H
AU  - Bassett JH
AD  - MRC Molecular Endocrinology Group, MRC Clinical Sciences Centre, Imperial School 
      of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom.
FAU - Forbes, S A
AU  - Forbes SA
FAU - Pannett, A A
AU  - Pannett AA
FAU - Lloyd, S E
AU  - Lloyd SE
FAU - Christie, P T
AU  - Christie PT
FAU - Wooding, C
AU  - Wooding C
FAU - Harding, B
AU  - Harding B
FAU - Besser, G M
AU  - Besser GM
FAU - Edwards, C R
AU  - Edwards CR
FAU - Monson, J P
AU  - Monson JP
FAU - Sampson, J
AU  - Sampson J
FAU - Wass, J A
AU  - Wass JA
FAU - Wheeler, M H
AU  - Wheeler MH
FAU - Thakker, R V
AU  - Thakker RV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (DNA Transposable Elements)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 11
MH  - DNA Transposable Elements
MH  - Exons
MH  - Female
MH  - Humans
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - *Mutation
MH  - Neoplasm Proteins/*genetics
MH  - Pedigree
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - *Proto-Oncogene Proteins
MH  - Sequence Deletion
PMC - PMC1376903
EDAT- 1998/04/16 02:03
MHDA- 2000/03/21 09:00
PMCR- 1998/08/01
CRDT- 1998/04/16 02:03
PHST- 1998/04/16 02:03 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1998/04/16 02:03 [entrez]
PHST- 1998/08/01 00:00 [pmc-release]
AID - S0002-9297(07)63487-9 [pii]
AID - 10.1086/301729 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1998 Feb;62(2):232-44. doi: 10.1086/301729.