Frequent Large Germline HRPT2 Deletions in a French National Cohort of Patients With Primary Hyperparathyroidism
Frequent Large Germline HRPT2 Deletions in a French National Cohort of Patients With Primary Hyperparathyroidism
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DOI：
10.1210/jc.2012-2789
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发表时间：
2013-02-01
影响因子：
5.8
通讯作者：
Groussin, Lionel
中科院分区：
文献类型：
--
作者：
Bricaire, Leopoldine;Odou, Marie-Francoise;Groussin, Lionel
内容：高甲状旁腺-颌骨肿瘤综合征（hyperparathyrophilm-jaw tumor syndrome，HPT-JT）是一种常染色体显性遗传的综合征，可合并甲状旁腺腺瘤或癌、颌骨纤维骨肿瘤、囊性肾病变和子宫肿瘤。在约50%-75%的HPT-JT病例和约14%的家族性孤立性甲状旁腺功能亢进症中鉴定出编码副纤维蛋白的HRPT 2基因（CDC 73）的种系突变。一个完整的删除该基因最近已被报道在1散发病例和家庭提出HPT-JT.Objective：本研究的目的是报告分子异常的HRPT 2基因的患者原发性甲状旁腺功能亢进症在法国国家队列从Groupe d 'Etude des Tumeurs内分泌。患者的基因组DNA进行筛选，通过PCR为基础的测序影响HRPT 2和实时定量PCR分析的点突变的总deletions.Results：我们报告了20个索引患者的老年HRPT 2异常。诊断原发性甲状旁腺功能亢进的中位年龄为23岁（范围14-65岁）。诊断时的中位血清总钙水平为3.19 mmol/L（范围2.8-4.3 mmol/L）。通过常规测序鉴定了13种不同的突变，包括7种从未报道的突变。7例患者（35%）携带该基因的总缺失（3例完全缺失和4例部分缺失）。未发现基因型-表型相关性。总缺失的HRPT 2基因被确定在7%的患者，其中一个常规的筛查直接测序来了作为negative.Conclusion：总缺失分析的HRPT 2基因是指所有患者阴性的突变，提出与HPT-JT或家族孤立性甲状旁腺功能亢进，甲状旁腺癌，或在患者明显散发甲状旁腺腺瘤诊断在一个年轻的年龄，有严重的高钙血症。（临床内分泌代谢杂志98：E403-E408，2013）
Context: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant syndrome with incomplete penetrance that can associate in a single patient parathyroid adenoma or carcinoma, fibro-osseous jaw tumor, cystic kidney lesion, and uterine tumor. Germline mutations of the HRPT2 gene (CDC73) coding for parafibromin are identified in approximately 50%-75% of HPT-JT cases and in approximately 14% of familial isolated hyperparathyroidism. A whole deletion of this gene has recently been reported in 1 sporadic case and in a family presenting with HPT-JT.Objective: The objective of the study was to report molecular abnormalities of the HRPT2 gene in patients with primary hyperparathyroidism in a French National cohort from the Groupe d'Etude des Tumeurs Endocrines.Methods: Patients' genomic DNA was screened by PCR-based sequencing for point mutations affecting HRPT2 and real-time quantitative PCR analysis for gross deletions.Results: We report 20 index patients with a germinal HRPT2 abnormality. Median age at diagnosis of primary hyperparathyroidism was 23 years (range 14-65 years). Median serum total calcium level at diagnosis was 3.19 mmol/L (range 2.8-4.3 mmol/L). Thirteen different mutations were identified by routine sequencing, including 7 mutations never reported. Seven patients (35%) carried a gross deletion of this gene (3 complete and 4 partial deletions). No genotype-phenotype correlation could be identified. Agross deletion of the HRPT2 gene was identified in 7% of patients for whom a routine screening by direct sequencing came up as negative.Conclusion: Gross deletion analysis of the HRPT2 gene is indicated for all patients negative for mutation, presenting with HPT-JT or familial isolated hyperparathyroidism, parathyroid carcinoma, or in patients with apparently sporadic parathyroid adenoma diagnosed at a young age, having a severe hypercalcemia. (J Clin Endocrinol Metab 98: E403-E408, 2013)