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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0066v1 15/4/1115    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Masi, G. Articles by Palu, G. Search for Related Content PubMed PubMed Citation Articles by Masi, G. Articles by Palu, G.

G Masi, IRCSS Istituto Oncologico Veneto, Padova, Italy
L Barzon, Dept of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padua, Italy
M Iacobone, Dept of Surgical and Gastroenterological Sciences- Endocrine Surgery Unit, University of Padova, Padova, Italy
G Viel, Dept of Surgical and Gastroenterological Sciences- Endocrine Surgery Unit, University of Padova, Padova, Italy
A Porzionato, Dept of Human Anatomy and Physiology, University of Padova, Padova, Italy
V Macchi, Padova, United Kingdom
R De Caro, Dept of Human Anatomy and Physiology, University of Padova, Padova, Italy
G Favia, Padova, Italy
G Palu, Padova, Italy

Correspondence: Luisa Barzon, Email: luisa.barzon{at}unipd.it

Abstract

HRPT2 germline mutations are responsible for more than half of cases of hyperparathyroidism-jaw tumor syndrome (HPT-JT) and for a subset of familial isolated hyperparathyroidism (FIHP). We performed a clinical, genetic, and histopathologic study in three unrelated Italian kindreds with HPT-JT and FIHP. We identified three germline inactivating mutations of the HRPT2 gene in the probands and affected patients of the three kindreds, but also in some asymptomatic subjects. HPT-JT and FIHP patients had similar laboratory, clinical, and demographic features and shared primary hyperparathyroidism and other neoplasms, the most common of which was uterine polyposis. Genetic analysis of tumor samples demonstrated a second somatic HRPT2 mutation only in a parathyroid adenoma and no cases with loss of the wild-type allele or methylation of the HRPT2 promoter, even though immunohistochemical analysis demonstrated loss of nuclear parafibromin expression in all tumors, including a uterine polyp. In conclusion, our results indicate that FIHP and HPT-JT associated with HRPT2 mutations do not have distinct clinical, genetic, and histopathologic features, but may represent variants of the same genetic disease. This study also confirms that uterine involvement represents a clinical manifestation of the syndrome.