Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Hum Mutat. 2010 Mar;31(3):295-307. doi: 10.1002/humu.21188.
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 beta-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.
甲状旁腺功能亢进-颌骨肿瘤（HPT-JT）综合征是一种常染色体显性遗传病，其特征是甲状旁腺瘤与上颌骨和/或下颌骨的骨化纤维瘤同时发生。负责 HPT-JT 的基因，称为 CDC73，于 2002 年被确定，并编码一种 531 个氨基酸的蛋白，称为副纤维蛋白。副纤维蛋白主要是一种核蛋白，它与β-连环蛋白直接相互作用，并且还构成 RNA 聚合酶相关因子-1 复合物（Paf1C）的一部分，该复合物调节转录。在大多数 HPT-JT 患者中检测到杂合性生殖系 CDC73 突变，并且在受影响个体的肿瘤中检测到 CDC73 基因座的杂合性丢失（LOH）与肿瘤抑制因子的作用一致。体细胞 CDC73 突变是常见的非家族性（即散发性）甲状旁腺癌，也已在良性散发性甲状旁腺瘤以及散发性肾和纤维骨性颌骨肿瘤中报道。迄今为止，已经确定了 111 个独立的 CDC73 突变（68 个生殖系；38 个体细胞；5 个未定义），这些突变发生在 CDC73 基因的整个编码区和剪接位点，大多数（>80%）预测副纤维蛋白的过早截断。这些 CDC73 突变及其临床和生物学相关性进行了综述。
