PMID- 18084346
OWN - NLM
STAT- MEDLINE
DCOM- 20080130
LR  - 20211027
IS  - 1745-8374 (Electronic)
IS  - 1745-8366 (Linking)
VI  - 4
IP  - 1
DP  - 2008 Jan
TI  - Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 
      gene.
PG  - 53-8
AB  - BACKGROUND: Familial isolated primary hyperparathyroidism (FIHP) is an autosomal 
      dominant disorder that can represent an early stage of either the multiple 
      endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumor (HPT-JT) 
      syndromes; alternatively, the condition can be caused by an allelic variant of 
      MEN1 or HRPT2 (hyperparathyroidism 2 gene), or caused by a distinct entity 
      involving another locus. We have explored these possibilities in a patient with 
      primary hyperparathyroidism, whose mother had a history of renal calculi and 
      primary hyperparathyroidism. INVESTIGATIONS: Serum biochemistry and radiological 
      investigations for primary hyperparathyroidism, MEN1 and HPT-JT, and genetic 
      testing for MEN1 and HRPT2 mutations were undertaken. DIAGNOSIS: FIHP with 
      primary hyperparathyroidism as the sole endocrinopathy due to a previously 
      unreported heterozygous missense germline MEN1 mutation, Tyr351Asn. In addition, 
      another unreported heterozygous missense germline MEN1 mutation, Trp220Leu, was 
      identified in an unrelated male patient with FIHP, whose mother and sister also 
      had primary hyperparathyroidism. DNA from a parathyroid tumor from the sister 
      revealed a loss of heterozygosity in which the mutant allele was retained. This 
      is consistent with Knudson's 'two-hit' model of hereditary cancer and a tumor 
      suppressor role for MEN1 in FIHP. MANAGEMENT: The patient underwent 
      parathyroidectomy and has remained normocalcemic over a follow-up period of 6 
      years. The other four patients have remained normocalcemic for a follow-up period 
      of 4-15 years following parathyroidectomy. None has developed abnormalities of 
      the MEN1 syndrome, providing further support that FIHP is a distinct genetic 
      variant of the MEN1 syndrome.
FAU - Hannan, Fadil M
AU  - Hannan FM
AD  - Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of 
      Oxford, Churchill Hospital, Oxford, UK.
FAU - Nesbit, M Andrew
AU  - Nesbit MA
FAU - Christie, Paul T
AU  - Christie PT
FAU - Fratter, Carl
AU  - Fratter C
FAU - Dudley, Nicholas E
AU  - Dudley NE
FAU - Sadler, Greg P
AU  - Sadler GP
FAU - Thakker, Rajesh V
AU  - Thakker RV
LA  - eng
GR  - G84/6423/MRC_/Medical Research Council/United Kingdom
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nat Clin Pract Endocrinol Metab
JT  - Nature clinical practice. Endocrinology & metabolism
JID - 101261798
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Female
MH  - Humans
MH  - Hyperparathyroidism/diagnosis/*genetics/surgery
MH  - Loss of Heterozygosity
MH  - Male
MH  - Mutation/*genetics
MH  - Parathyroidectomy
MH  - Proto-Oncogene Proteins/*genetics
EDAT- 2007/12/18 09:00
MHDA- 2008/01/31 09:00
CRDT- 2007/12/18 09:00
PHST- 2007/07/10 00:00 [received]
PHST- 2007/11/02 00:00 [accepted]
PHST- 2007/12/18 09:00 [pubmed]
PHST- 2008/01/31 09:00 [medline]
PHST- 2007/12/18 09:00 [entrez]
AID - ncpendmet0718 [pii]
AID - 10.1038/ncpendmet0718 [doi]
PST - ppublish
SO  - Nat Clin Pract Endocrinol Metab. 2008 Jan;4(1):53-8. doi: 10.1038/ncpendmet0718.