Hormones and Cancer

, Volume 3, Issue 1, pp 44–51

Frequent Germ-Line Mutations of the MEN1, CASR, and HRPT2/CDC73 Genes in Young Patients with Clinically Non-familial Primary Hyperparathyroidism

Authors

  • Lee F. Starker
    • Department of SurgeryYale University School of Medicine
    • Yale Endocrine Neoplasia LaboratoryYale University School of Medicine
    • Department of Surgical SciencesUppsala University
  • Tobias Åkerström
    • Department of SurgeryYale University School of Medicine
    • Yale Endocrine Neoplasia LaboratoryYale University School of Medicine
  • William D. Long
    • Department of SurgeryYale University School of Medicine
    • Yale Endocrine Neoplasia LaboratoryYale University School of Medicine
  • Alberto Delgado-Verdugo
    • Yale Endocrine Neoplasia LaboratoryYale University School of Medicine
    • Department of Surgical SciencesUppsala University
  • Patricia Donovan
    • Department of SurgeryYale University School of Medicine
  • Robert Udelsman
    • Department of SurgeryYale University School of Medicine
  • Richard P. Lifton
    • Department of GeneticsYale University School of Medicine
    • Department of SurgeryYale University School of Medicine
    • Yale Endocrine Neoplasia LaboratoryYale University School of Medicine
    • Cancer Genetics and Genomics Program, Yale Cancer CenterYale University School of Medicine
Article

DOI: 10.1007/s12672-011-0100-8

Cite this article as:
Starker, L.F., Åkerström, T., Long, W.D. et al. HORM CANC (2012) 3: 44. doi:10.1007/s12672-011-0100-8

Abstract

Familial primary hyperparathyroidism (FPHPT) may occur due to an underlying germ-line mutation in the MEN1, CASR, or HRPT2/CDC73 genes. The disease may be undiagnosed in the absence of a history suggestive of FHPT. Young PHPT patients (≤45 years of age) are more likely to harbor occult FPHPT. A total of 1,161 (136 were ≤45 years of age) PHPT patients underwent parathyroidectomy from 2001 to 2009. Thirty-four patients declined participation. Sixteen patients were diagnosed in the clinical routine with FPHPT (11 MEN1, four MEN2A, and one HPT-JT) and were not included in the genetic analysis. Eighty-six young (≤45 years of age) patients with clinically non-syndromic PHPT underwent genetic analysis. Sanger sequencing of all coding regions of the MEN1, CASR, and the HRPT2/CDC73 genes was performed. Eight of 86 (9.3%) young patients with clinically non-familial PHPT displayed deleterious germ-line mutations in the susceptibility genes (4 MEN1, 3 CASR, and 1 HRPT2/CDC73). There was one insertion, one deletion, two nonsense, and four missense mutations, all predicted to be highly damaging to protein function and absent in 3,244 control chromosomes. Germ-line mutations in known susceptibility genes within young patients with PHPT, including those diagnosed in the clinical routine, was 24/102 (23.5%; 15 MEN1, four RET, three CASR, and two HRPT2/CDC73). We demonstrate that germ-line inactivating mutations in susceptibility genes are common in young patients with clinically non-familial PHPT. Thus, enhanced use of genetic analysis may be warranted in clinically non-familial young PHPT patients.

Keywords

HyperparathyroidismMEN1ParathyroidFamilial syndromes

Supplementary material

12672_2011_100_MOESM1_ESM.docx (173 kb)
ESM 1(DOCX 172 kb)

Copyright information

© Springer Science+Business Media, LLC 2011