Endocrine Practice, Molecular Laboratory, Brückenstr.21, 69120 Heidelberg, Germany.
Eur J Endocrinol. 2011 Sep;165(3):477-83. doi: 10.1530/EJE-11-0003. Epub 2011 Jun 7.
Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of benign and malignant parathyroid tumours, ossifying jaw tumours, various cystic and neoplastic renal abnormalities and benign and malignant uterine tumours. Disease-causing mutations have been localised in the tumour suppressor gene CDC73. There is limited information available on the mutations, and resulting phenotypes and long-term follow-up data are especially scarce.
We analysed the clinical data from 16 patients (including three families) carrying mutations in the CDC73 gene. We describe five new mutations/gene variants, the corresponding phenotypes of these carriers and the long-term follow-up.
The 16 patients were evaluated at an endocrine outpatient clinic and at a surgical department. DNA samples were obtained for sequence analysis of the CDC73 gene.
Clinical features of HPT-JT syndrome were detected in 13 of the 15 carriers with germline CDC73 mutations. The major features were benign (n=7; 47%) or cancerous (n=3; 20%) HPT-JT was present in eight cases (53%). Most patients had severe hypercalcaemia, and median serum calcium levels were 3.36 mmol/l. A patient with non-secretory parathyroid carcinoma was included. HPT was diagnosed at a median age of 28.5 years. Mutational analysis of the CDC73 gene identified eight sequence changes, three of them have been reported previously, whereas five are novel: c.1346delG, c.88_94delTTCTCCT, the non-coding variants, c.307+5G>T and c.424-5T>C and c.*12C>A of unknown significance.
This study significantly increases the information available on the mutations and phenotypes of HPT-JT syndrome.
甲状旁腺-颌骨肿瘤（HPT-JT）综合征是一种罕见的常染色体显性遗传疾病，可导致良性和恶性甲状旁腺肿瘤、骨化性颌骨肿瘤、各种囊性和肿瘤性肾脏异常以及良性和恶性子宫肿瘤。致病突变已定位在肿瘤抑制基因 CDC73 中。关于这些突变及其导致的表型和长期随访数据的信息有限。
我们分析了携带 CDC73 基因突变的 16 名患者（包括 3 个家系）的临床数据。我们描述了 5 种新的突变/基因变异、这些携带者的相应表型和长期随访情况。
对 16 名患者进行了内分泌门诊和外科部门的评估。采集 DNA 样本进行 CDC73 基因序列分析。
在 15 名具有种系 CDC73 突变的携带者中，有 13 名检测到 HPT-JT 综合征的临床特征。主要特征为良性（n=7；47%）或恶性（n=3；20%）HPT-JT 见于 8 例（53%）。大多数患者存在严重高钙血症，中位数血清钙水平为 3.36mmol/L。包括一名非分泌性甲状旁腺癌患者。HPT 的诊断中位年龄为 28.5 岁。CDC73 基因突变分析发现了 8 个序列变化，其中 3 个以前已有报道，而 5 个是新的：c.1346delG、c.88_94delTTCTCCT、非编码变异 c.307+5G>T 和 c.424-5T>C 以及意义不明的 c.*12C>A。
本研究显著增加了关于 HPT-JT 综合征突变和表型的信息。
