This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moon, S.-D. Articles by Cha, B.-Y. Search for Related Content PubMed PubMed Citation Articles by Moon, S.-D. Articles by Cha, B.-Y. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM UniGene Substance via MeSH Related Collections Calcium and Bone Metabolism Endocrine Oncology

A Novel IVS2-1G>A Mutation Causes Aberrant Splicing of the HRPT2 Gene in a Family with Hyperparathyroidism-Jaw Tumor Syndrome

Departments of Internal Medicine (S.-D.M., J.-H.K., J.-H.H., S.-J.Y., K.-H.Y., M.-I.K., K.-W.L., H.-Y.S., S.-K.K., B.-Y.C.) and Clinical Pathology (K.-M.K.), and Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Science, Department of Biomedical Sciences (E.-M.K., S.-J.K.Y.), The Catholic University of Korea College of Medicine, Seoul, 137-701 Korea; Korean Hereditary Tumor Registry (J.-H.P., J.-G.P., I.-J.K., H.C.K.), Laboratory of Cell Biology, Cancer Research Center and Cancer Research Institute, Seoul National University, Seoul, 151-742 Korea; Research Institute and Hospital (J.-G.P.), National Cancer Center, Goyang, Gyeonggi, 411-769 Korea; Departments of Pathology (S.-W.H.) and Internal Medicine (K.-R.K.), Yonsei University College of Medicine, Seoul, 120-749 Korea; and Departments of Internal Medicine (S.-D.M., J.-H.H.) and Surgery (S.-J.O.), Our Lady of Mercy Hospital, The Catholic University of Korea College of Medicine, Incheon, 403-720 Korea

Address all correspondence and requests for reprints to: Dr. Je-Ho Han, Division of Endocrinology and Metabolism, Department of Internal Medicine, Our Lady of Mercy Hospital, The Catholic University of Korea College of Medicine, 665 Pupyung-dong Pupyung-gu, Incheon 403-720, Korea. E-mail: hjh60103{at}dreamwiz.com.

HRPT2, the gene associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, was previously mapped to 1q24-q32. It was recently cloned, and several germline mutations were found to predispose to HPT-JT syndrome. We sequenced the complete HRPT2 coding sequence and splice-junctional regions in a Korean family with HPT-JT syndrome and identified a novel germline mutation, IVS2-1G>A in intron 2, that caused the autosomal dominant trait of HPT-JT syndrome in this family. RT-PCR and sequencing of the transcripts revealed that this splicing mutation generated alternative splicing errors leading to the formation of two different transcripts, one with exon 3 deleted, the other lacking the first 23 bp of exon 3 due to the use of an internal splice acceptor in exon 3. Translation of both transcripts results in premature termination. In addition, we detected two novel somatic mutations of HRPT2 in malignant parathyroid tumors from the affected individuals. One, 85delG, causes premature termination; the other, an 18 bp in-frame deletion of 13_30delCTTAGCGTCCTGCGACAG, suggests that this region may be important in the development of the parathyroid carcinomas in HPT-JT syndrome. These findings provide further evidence that mutation of HRPT2 is associated with the formation of parathyroid tumors in HPT-JT syndrome.

This article has been cited by other articles:

				A. Ghosh, H. Kuppusamy, and L. M. Pilarski Aberrant Splice Variants of HAS1 (Hyaluronan Synthase 1) Multimerize with and Modulate Normally Spliced HAS1 Protein: A POTENTIAL MECHANISM PROMOTING HUMAN CANCER J. Biol. Chem., July 10, 2009; 284(28): 18840 - 18850. [Abstract] [Full Text] [PDF]

				M. A Hahn, J. McDonnell, and D. J Marsh The effect of disease-associated HRPT2 mutations on splicing J. Endocrinol., June 1, 2009; 201(3): 387 - 396. [Abstract] [Full Text] [PDF]

				S. Adamia, A. A. Reichert, H. Kuppusamy, J. Kriangkum, A. Ghosh, J. J. Hodges, P. M. Pilarski, S. P. Treon, M. J. Mant, T. Reiman, et al. Inherited and acquired variations in the hyaluronan synthase 1 (HAS1) gene may contribute to disease progression in multiple myeloma and Waldenstrom macroglobulinemia Blood, December 15, 2008; 112(13): 5111 - 5121. [Abstract] [Full Text] [PDF]

				G. Masi, L. Barzon, M. Iacobone, G. Viel, A. Porzionato, V. Macchi, R. De Caro, G. Favia, and G. Palu Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism Endocr. Relat. Cancer, December 1, 2008; 15(4): 1115 - 1126. [Abstract] [Full Text] [PDF]

				F Cetani, E Pardi, E Ambrogini, P Viacava, S Borsari, M Lemmi, L Cianferotti, P Miccoli, A Pinchera, A Arnold, et al. Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation Endocr. Relat. Cancer, June 1, 2007; 14(2): 493 - 499. [Abstract] [Full Text] [PDF]

				V. M. Howell, J. W. Cardinal, A.-L. Richardson, O. Gimm, B. G. Robinson, and D. J. Marsh Rapid Mutation Screening for HRPT2 and MEN1 Mutations Associated with Familial and Sporadic Primary Hyperparathyroidism J. Mol. Diagn., November 1, 2006; 8(5): 559 - 566. [Abstract] [Full Text] [PDF]

				V. Guarnieri, A. Scillitani, L. A. Muscarella, C. Battista, N. Bonfitto, M. Bisceglia, S. Minisola, M. L. Mascia, L. D'Agruma, and D. E. C. Cole Diagnosis of Parathyroid Tumors in Familial Isolated Hyperparathyroidism with HRPT2 Mutation: Implications for Cancer Surveillance J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2827 - 2832. [Abstract] [Full Text] [PDF]

				C Juhlin, C Larsson, T Yakoleva, I Leibiger, B Leibiger, A Alimov, G Weber, A Hoog, and A Villablanca Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr. Relat. Cancer, June 1, 2006; 13(2): 509 - 523. [Abstract] [Full Text] [PDF]