PMID- 12699448
OWN - NLM
STAT- MEDLINE
DCOM- 20030613
LR  - 20190813
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 58
IP  - 5
DP  - 2003 May
TI  - Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial 
      isolated primary hyperparathyroidism.
PG  - 639-46
AB  - BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is an autosomal dominant 
      disorder characterized by uniglandular or multiglandular parathyroid tumours that 
      occur in the absence of other endocrine tumours. The disorder may represent 
      either an early stage of multiple endocrine neoplasia type 1 (MEN1), or an 
      allelic variant of MEN1, or a distinct entity involving another locus. We have 
      explored these possibilities in seven families in whom primary 
      hyperparathyroidism occurred as the sole endocrinopathy. METHODS: Seven FIHP 
      families were ascertained and venous blood samples obtained from 35 members (17 
      affected and 18 unaffected) for DNA sequence analysis of the MEN1 gene. The mean 
      (+/- SD) follow-up period in the 17 affected members was 15.06 (+/- 8.83) years. 
      RESULTS: Four heterozygous germline mutations of the MEN1 gene were identified. 
      These consisted of two 4-bp intragenic deletions that would result in prematurely 
      truncated proteins, and two missense (Asp153Val and Ala411Pro) mutations. 
      Furthermore, analysis of parathyroid tumour DNA from one individual revealed a 
      loss of the wild-type allele and retention of the mutant allele, consistent with 
      Knudson's 'two-hit' model of hereditary cancer and a tumour suppressor role for 
      MEN1 in FIHP. CONCLUSIONS: Our results provide further support for FIHP being a 
      distinct allelic variant of MEN1, and an analysis of the 16 mutations reported to 
      date indicate that FIHP is associated with a higher frequency of missense MEN1 
      mutations.
FAU - Pannett, A A J
AU  - Pannett AA
AD  - MRC Molecular Endocrinology Group, MRC Clinical Sciences Centre, Imperial College 
      School of Medicine, Hammersmith Hospital, London, UK.
FAU - Kennedy, A M
AU  - Kennedy AM
FAU - Turner, J J O
AU  - Turner JJ
FAU - Forbes, S A
AU  - Forbes SA
FAU - Cavaco, B M
AU  - Cavaco BM
FAU - Bassett, J H D
AU  - Bassett JH
FAU - Cianferotti, L
AU  - Cianferotti L
FAU - Harding, B
AU  - Harding B
FAU - Shine, B
AU  - Shine B
FAU - Flinter, F
AU  - Flinter F
FAU - Maidment, C G H
AU  - Maidment CG
FAU - Trembath, R
AU  - Trembath R
FAU - Thakker, R V
AU  - Thakker RV
LA  - eng
PT  - Journal Article
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Parathyroid Hormone)
SB  - IM
MH  - Adenoma/genetics
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Family Health
MH  - Female
MH  - Gene Deletion
MH  - Germ-Line Mutation/*genetics
MH  - Humans
MH  - Hyperparathyroidism/*genetics
MH  - Hyperplasia
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Mutation, Missense/genetics
MH  - Parathyroid Glands/pathology
MH  - Parathyroid Hormone/blood
MH  - Parathyroid Neoplasms/*genetics/pathology
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Sequence Analysis, DNA/methods
EDAT- 2003/04/18 05:00
MHDA- 2003/06/14 05:00
CRDT- 2003/04/18 05:00
PHST- 2003/04/18 05:00 [pubmed]
PHST- 2003/06/14 05:00 [medline]
PHST- 2003/04/18 05:00 [entrez]
AID - 1765 [pii]
AID - 10.1046/j.1365-2265.2003.01765.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2003 May;58(5):639-46. doi: 
      10.1046/j.1365-2265.2003.01765.x.