Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
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DOI：
10.1186/s13053-016-0053-6
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发表时间：
2016-06-08
影响因子：
1.7
通讯作者：
Hansen, Thomas v. O.
中科院分区：
文献类型：
--
作者：
Bennedbaek, Marc;Rossing, Maria;Hansen, Thomas v. O.
背景：琥珀酸脱氢酶复合物基因SDHB、SDHC和SDHD的种系突变易导致嗜铬细胞瘤和副神经节瘤。在这里，我们通过筛选143名丹麦嗜铬细胞瘤和副神经节瘤患者来研究丹麦人群中的SDHB、SDHC和SDHD突变谱。方法：采用Sanger测序或下一代测序进行突变筛选。使用Exome Aggregation Consortium数据库确定未知临床意义变异的频率，例如内含子、错义和同义变异，而错义突变的意义则通过计算机分析和杂合缺失分析来预测。结果：我们报告了18种系变异；SDHB组9人，SDHC组6人，SDHD组3人。在这18种变体中，有8种是新颖的。我们将12种变异分类为可能致病性/致病性，1种可能为良性，5种为临床意义未知的变异。结论：识别和分类丹麦人群中存在的SDHB、SDHC和SDHD变异将增加对这些基因变异的日益增长的知识，并可能支持未来的临床风险评估。
Background: Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma patients.Methods: Mutational screening was performed by Sanger sequencing or next-generation sequencing. The frequencies of variants of unknown clinical significance, e.g. intronic, missense, and synonymous variants, were determined using the Exome Aggregation Consortium database, while the significance of missense mutations was predicted by in silico and loss of heterozygosity analysis when possible.Results: We report 18 germline variants; nine in SDHB, six in SDHC, and three in SDHD. Of these 18 variants, eight are novel. We classify 12 variants as likely pathogenic/pathogenic, one as likely benign, and five as variants of unknown clinical significance.Conclusions: Identifying and classifying SDHB, SDHC, and SDHD variants present in the Danish population will augment the growing knowledge on variants in these genes and may support future clinical risk assessments.