VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype
VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype
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DOI：
10.1038/ejhg.2013.279
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发表时间：
2014-09-01
影响因子：
5.2
通讯作者：
Pigny, Pascal
中科院分区：
文献类型：
--
作者：
Coppin, Lucie;Grutzmacher, Claudine;Pigny, Pascal
通过传统的Sanger测序鉴定Von Hippel-Lindau （VHL）镶嵌突变需要一个劳动密集型的富集步骤，从而解释了镶嵌现象在患者中的发生被低估了。如今，通过下一代测序（NGS）可以检测细胞亚群中的突变。在这里，我们描述了一种使用NGS高覆盖率的诊断策略，这些患者通过Sanger测序和缺失搜索均为VHL异常阴性。在两例患者中，NGS检测到VHL的马赛克突变。一名等位基因突变频率为5.7%的患者具有严重的表型和早期发病。总之，医院肿瘤分子遗传学实验室的临床NGS是鉴定VHL嵌合体突变的有效工具。它的使用可以改善病人的监测和遗传咨询。
The identification of Von Hippel-Lindau (VHL) mosaic mutations by conventional Sanger sequencing requires a labour-intensive enrichment step, thus explaining that mosaicism occurrence is underestimated in patients. Nowadays, it is possible to detect mutation in cell sub-populations by next-generation sequencing (NGS). Here, we described a diagnosis strategy using NGS with high coverage in a series of eight patients who were negative for a VHL abnormality by Sanger sequencing and deletion search. In two patients, a mosaic mutation in VHL was detected by NGS. One patient with a 5.7% mutated allele frequency had a severe phenotype and an early disease onset. In conclusion, clinical NGS in an hospital molecular oncogenetics laboratory is an efficient tool to identify VHL mosaic mutation. Its use may improve patient monitoring and genetic counseling.