PMID- 14715834
OWN - NLM
STAT- MEDLINE
DCOM- 20040211
LR  - 20230411
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 89
IP  - 1
DP  - 2004 Jan
TI  - Familial isolated hyperparathyroidism is rarely caused by germline mutation in 
      HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome.
PG  - 96-102
AB  - Familial isolated hyperparathyroidism (FIHP) can result occasionally from the 
      incomplete expression of a syndromic form of familial hyperparathyroidism (HPT), 
      specifically multiple endocrine neoplasia type 1 (MEN1), familial hypocalciuric 
      hypercalcemia, or the hyperparathyroidism-jaw tumor syndrome (HPT-JT). The cause 
      of FIHP has not been identified in the majority of families. We investigated 32 
      families with FIHP to determine the frequency of occult mutation in HRPT2, the 
      gene causing HPT-JT. All families had negative clinical testing for MEN1, 
      hypocalciuric hypercalcemia, and HPT-JT and negative mutational screening of MEN1 
      and CASR, the gene for the calcium-sensing receptor. Thus, an extended effort was 
      made to exclude each of the principal syndromic causes of FIHP. The families were 
      characterized by young probands (42 +/- 3 yr) and occasionally unusual 
      parathyroid histology, including four families with one case of parathyroid 
      cancer. We had speculated that there was a high frequency of occult mutation in 
      HRPT2 among such carefully screened kindreds. This hypothesis became testable 
      with the recent identification of that gene. Among the 32 FIHP families, only a 
      single one was found to have a mutation in HRPT2 (679insAG); this mutation 
      predicts premature truncation of its gene product, parafibromin, and thus its 
      presumed inactivation. Even accounting for families with one of the three occult 
      syndromes and false negative biochemical or DNA testing, these results indicate 
      that an unexpectedly large fraction of FIHP has currently unrecognized causes.
FAU - Simonds, William F
AU  - Simonds WF
AD  - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. 
      wsf@helix.nih.gov
FAU - Robbins, Christiane M
AU  - Robbins CM
FAU - Agarwal, Sunita K
AU  - Agarwal SK
FAU - Hendy, Geoffrey N
AU  - Hendy GN
FAU - Carpten, John D
AU  - Carpten JD
FAU - Marx, Stephen J
AU  - Marx SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (CDC73 protein, human)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Female
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Hyperparathyroidism/*genetics
MH  - Jaw Neoplasms/*genetics
MH  - Male
MH  - Middle Aged
MH  - Parathyroid Glands/pathology
MH  - Parathyroid Neoplasms/pathology
MH  - Pedigree
MH  - Proteins/*genetics
MH  - Syndrome
MH  - Tumor Suppressor Proteins
EDAT- 2004/01/13 05:00
MHDA- 2004/02/12 05:00
CRDT- 2004/01/13 05:00
PHST- 2004/01/13 05:00 [pubmed]
PHST- 2004/02/12 05:00 [medline]
PHST- 2004/01/13 05:00 [entrez]
AID - 10.1210/jc.2003-030675 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2004 Jan;89(1):96-102. doi: 10.1210/jc.2003-030675.