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Cell division cycle protein 73 homolog ( CDC73 ) mutations in the hyperparathyroidism‐jaw tumor syndrome (HPT‐JT) and parathyroid tumors
Author(s) -
Newey Paul J.,
Bowl Michael R.,
Cranston Treena,
Thakker Rajesh V.
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21188
Subject(s) - biology , hyperparathyroidism , parathyroid neoplasm , cancer research , genetics , endocrinology , parathyroid adenoma
The hyperparathyroidism‐jaw tumor (HPT‐JT) syndrome is an autosomal dominant disorder characterized by the occurrence of parathyroid tumors in association with ossifying fibromas of the maxilla and/or mandible. The gene responsible for HPT‐JT, known as CDC73 , was identified in 2002 and encodes a 531 amino acid protein known as parafibromin. Parafibromin is predominantly a nuclear protein that interacts directly with β‐catenin and also forms part of the RNA polymerase associated factor‐1 complex (Paf1C) that regulates transcription. Heterozygous germline CDC73 mutations are detected in the majority of patients with HPT‐JT, and the demonstration of loss of heterozygosity (LOH) at the CDC73 locus in tumors from affected individuals is consistent with a tumor suppressor role. Somatic CDC73 mutations are a frequent finding in nonfamilial (i.e., sporadic) parathyroid carcinomas and have also been reported in benign sporadic parathyroid tumors as well as sporadic renal and fibro‐osseous jaw tumors. To date, 111 independent CDC73 mutations have been identified (68 germline; 38 somatic; 5 undefined), and these occur throughout the coding region and splice sites of the CDC73 gene, with the majority (>80%) predicting premature truncation of the parafibromin protein. These CDC73 mutations, together with their clinical and biological relevance, are reviewed. Hum Mutat 31:295–307, 2010. © 2010 Wiley‐Liss, Inc.