Abstract
Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease characterized by the occurrences of parathyroid tumors and ossifying fibroma of maxilla/mandible. It is caused by mutations in CDC73 gene and mutation carriers are at increased risk of parathyroid carcinoma. Hyperparathyroidism could be the sole manifestation. We reported two Chinese patients having parathyroid neoplasm with equivocal malignant potential and parathyroid carcinoma respectively with both germline and somatic CDC73 mutations detected. Both of them presented with severe hypercalcemia and primary hyperparathyroidism with no other HPT-JT associated tumors and negative family history. We identified one novel germline mutation CDC73 NM_024529.4: c.1475G > A; NP_078805.3: p.Trp492X and one novel somatic mutation CDC73 NM_024529.4: c.142G > T; NP_078805.3: p.Glu48X. The other germline mutation CDC73 NM_024529.4: c.226C > T; NP_078805.3: p.Arg76X and somatic mutation CDC73 NM_024529.4: c.85delG; NP_078805.3: p.Glu29SerfsX8 were previously reported. This is the first report of CDC73 mutations in the Chinese population. Genetic analysis is reliable to confirm the underlying hereditary basis of hyperparathyroidism. By identification of mutations, the patient and the family members could benefit from regular surveillance for early detection of tumors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Jackson CE, Norum RA, Boyd SB et al (1990) Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. Surgery 108:1006–1012
Teh BT, Farnebo F, Twigg S et al (1998) Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21–q32 in a subset of families. J Clin Endocrinol Metab 83:2114–2120
Szabo J, Heath B, Hill VM et al (1995) Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21–q31. Am J Hum Genet 56:944–950
Carpten JD, Robbins CM, Villablanca A et al (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32:676–680
Bradley KJ, Hobbs MR, Buley ID et al (2005) Uterine tumors are a phenotypic manifestation of the hyperparathyroidism-jaw tumor syndrome. J Intern Med 257:18–26
Bradley KJ, Cavaco BM, Bowl MR et al (2006) Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumors. Clin Endocrinol (Oxf) 64:299–306
Marx SJ (2000) Hyperparathyroid and hypoparathyroid disorders. N Engl J Med 343:1863–1875
Rozenblatt-Rosen O, Hughes CM, Nannepaga SJ et al (2005) The parafibromin tumor suppressor protein is part of a human Paf1 complex. Mol Cell Biol 25:612–620
Yart A, Gstaiger M, Wirbelauer C et al (2005) The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol 25:5052–5060
Cavaco BM, Barros L, Pannett AA et al (2001) The hyperparathyroidism-jaw tumor syndrome in a Portuguese kindred. QJM 94:213–222
Mizusawa N, Uchino S, Iwata T et al (2006) Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome. Clin Endocrinol (Oxf) 65:9–16
Moon SD, Park JH, Kim EM et al (2005) A Novel IVS2–1G>A mutation causes aberrant splicing of the HRPT2 gene in a family with hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 90:878–883
Shattuck TM, Valimaki S, Obara T et al (2003) Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 349:1722–1729
Howell VM, Haven CJ, Kahnoski K et al (2003) HRPT2 mutations are associated with malignancy in sporadic parathyroid tumors. J Med Genet 40:657–663
Newey PJ, Bowl MR, Cranston T et al (2010) Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors. Hum Mutat 31:295–307
Newey PJ, Bowl MR, Thakker RV (2009) Parafibromin–functional insights. J Intern Med 266:84–98
Rekik N, Ben Naceur B, Mnif M et al (2010) Hyperparathyroidism-jaw tumor syndrome: a case report. Ann Endocrinol (Paris) 71:121–126
Cetani F, Pardi E, Borsari S et al (2004) Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab 89:5583–5591
Iacobone M, Masi G, Barzon L et al (2009) Hyperparathyroidism-jaw tumor syndrome: a report of three large kindred. Langenbecks Arch Surg 394:817–825
Witteveen JE, Hamdy NA, Dekkers OM et al (2011) Downregulation of CASR expression and global loss of parafibromin staining are strong negative determinants of prognosis in parathyroid carcinoma. Mod Pathol 24:688–697
Shih RY, Fackler S, Maturo S et al (2009) Parathyroid carcinoma in multiple endocrine neoplasia type 1 with a classic germline mutation. Endocr Pract 15:567–572
Enomoto K, Uchino S, Ito A et al (2010) The surgical strategy and the molecular analysis of patients with parathyroid cancer. World J Surg 34:2604–2610
Haven CJ, van Puijenbroek M, Tan MH et al (2007) Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin Endocrinol (Oxf) 67:370–376
Guarnieri V, Scillitani A, Muscarella LA et al (2006) Diagnosis of parathyroid tumors in familial isolated hyperparathyroidism with HRPT2 mutation: implications for cancer surveillance. J Clin Endocrinol Metab 91:2827–2832
Acknowledgments
We thank the reviewer for the helpful comments to improve the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Siu, W.K., Law, C.Y., Lam, C.W. et al. Novel nonsense CDC73 mutations in Chinese patients with parathyroid tumors. Familial Cancer 10, 695–699 (2011). https://doi.org/10.1007/s10689-011-9466-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-011-9466-6