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This Article Full Text Full Text (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 Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Masi, G. Articles by Palù, G. Search for Related Content PubMed PubMed Citation Articles by Masi, G. Articles by Palù, G.

IRCCS-IOV (Istituto Oncologico Veneto), I-35128 Padova, Italy¹ Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Via A. Gabelli 63, I-35121 Padova, Italy² Endocrine Surgery Unit, Department of Surgical and Gastroenterological Sciences, University of Padova, I-35128 Padova, Italy³ Department of Human Anatomy and Physiology, University of Padova, I-35121 Padova, Italy

(Correspondence should be addressed to L Barzon; Email: luisa.barzon{at}unipd.it)

CDC73 (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 HPT (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 CDC73 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 HPT and other neoplasms, the most common of which was uterine polyposis. Genetic analysis of tumor samples demonstrated a second somatic CDC73 mutation only in a parathyroid adenoma and no cases with the loss of the wild-type allele or methylation of the CDC73 promoter, even though immunohistochemical analysis demonstrated the loss of nuclear parafibromin expression in all tumors, including a uterine polyp. In conclusion, our results indicate that FIHP and HPT-JT associated with CDC73 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.