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HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome

Carpten, JD; Robbins, CM; Villablanca, A; Forsberg, L; Presciuttini, S; Bailey-Wilson, J; Simonds, WF; Gillanders, EM; Kennedy, AM and Chen, JD, et al. (2002) In Nature Genetics 32(4). p.676-680
Abstract
We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls,... (More)
We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors. (Less)
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Nature Genetics
volume
32
issue
4
pages
676 - 680
publisher
Nature Publishing Group
external identifiers
  • wos:000179593000024
  • pmid:12434154
  • scopus:18744385803
ISSN
1546-1718
DOI
10.1038/ng1048
language
English
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yes
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7e566d4d-bbb5-483d-8ece-cf055181d971 (old id 322216)
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2007-08-13 14:20:45
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2017-12-10 04:30:01
@article{7e566d4d-bbb5-483d-8ece-cf055181d971,
  abstract     = {We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.},
  author       = {Carpten, JD and Robbins, CM and Villablanca, A and Forsberg, L and Presciuttini, S and Bailey-Wilson, J and Simonds, WF and Gillanders, EM and Kennedy, AM and Chen, JD and Agarwal, SK and Sood, R and Jones, MP and Moses, TY and Haven, C and Petillo, D and Leotlela, PD and Harding, B and Cameron, D and Pannett, AA and Hoog, A and Heath, H and James-Newton, LA and Robinson, B and Zarbo, RJ and Cavaco, BM and Wassif, W and Perrier, ND and Rosen, IB and Kristoffersson, Ulf and Turnpenny, PD and Farnebo, LO and Besser, GM and Jackson, CE and Morreau, H and Trent, JM and Thakker, RV and Marx, SJ and Teh, BT and Larsson, C and Hobbs, MR},
  issn         = {1546-1718},
  language     = {eng},
  number       = {4},
  pages        = {676--680},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome},
  url          = {http://dx.doi.org/10.1038/ng1048},
  volume       = {32},
  year         = {2002},
}