Abstract：
BACKGROUND: The von Hippel-Lindau (VHL) disease is a hereditary tumour syndrome caused by germline mutations in VHL tumour suppressor gene. The identification of VHL variants requires accurate classification which has an impact on patient management and genetic counselling.
METHODS: The TENGEN (French oncogenetics network of neuroendocrine tumors) and PREDIR (French National Cancer Institute network for Inherited predispositions to kidney cancer) networks have collected VHL genetic variants and clinical characteristics of all VHL-suspected patients analysed from 2003 to 2021 by one of the nine laboratories performing VHL genetic testing in France. Identified variants were registered in a locus-specific database, the Universal Mutation Database-VHL database (http://www.umd.be/VHL/).
RESULTS: Here we report the expert classification of 164 variants, including all missense variants (n=124), all difficult interpretation variants (n=40) and their associated phenotypes. After initial American College of Medical Genetics classification, first-round classification was performed by the VHL expert group followed by a second round for discordant and ambiguous cases. Overall, the VHL experts modified the classification of 87 variants including 30 variants of uncertain significance that were as (likely)pathogenic variants for 19, and as likely benign for 11.
CONCLUSIONS: Consequently, this work has allowed the diagnosis and influenced the genetic counselling of 45 VHL-suspected families and can benefit to the worldwide VHL community, through this review.
METHODS: The TENGEN (French oncogenetics network of neuroendocrine tumors) and PREDIR (French National Cancer Institute network for Inherited predispositions to kidney cancer) networks have collected VHL genetic variants and clinical characteristics of all VHL-suspected patients analysed from 2003 to 2021 by one of the nine laboratories performing VHL genetic testing in France. Identified variants were registered in a locus-specific database, the Universal Mutation Database-VHL database (http://www.umd.be/VHL/).
RESULTS: Here we report the expert classification of 164 variants, including all missense variants (n=124), all difficult interpretation variants (n=40) and their associated phenotypes. After initial American College of Medical Genetics classification, first-round classification was performed by the VHL expert group followed by a second round for discordant and ambiguous cases. Overall, the VHL experts modified the classification of 87 variants including 30 variants of uncertain significance that were as (likely)pathogenic variants for 19, and as likely benign for 11.
CONCLUSIONS: Consequently, this work has allowed the diagnosis and influenced the genetic counselling of 45 VHL-suspected families and can benefit to the worldwide VHL community, through this review.
摘要：
背景：vonHippel-Lindau（VHL）病是一种遗传性肿瘤综合征，由VHL抑癌基因的种系突变引起。VHL变异的鉴定需要准确的分类，这对患者管理和遗传咨询有影响。
方法：TENGEN（法国神经内分泌肿瘤肿瘤遗传学网络）和PREDIR（法国国家癌症研究所肾癌遗传易感性网络）网络收集了所有VHL的VHL遗传变异和临床特征。法国进行VHL基因测试的9个实验室之一从2003年到2021年进行了分析。识别的变异在基因座特异性数据库中注册，通用变异数据库-VHL数据库(http://www.umd.是/VHL/）。
结果：在这里，我们报告了164个变体的专家分类，包括所有错义变体(n=124)，所有难以解释的变异(n=40)及其相关表型。在最初的美国医学遗传学学院分类之后，VHL专家组进行了第一轮分类,随后对不一致和模棱两可的病例进行了第二轮分类.总的来说,VHL专家修改了87种变异的分类,包括30种具有不确定意义的变异,其中19种(可能)为致病性变异,11种可能为良性变异.
结论：因此，这项工作允许对45个VHL疑似家庭进行诊断并影响了遗传咨询，并可以使全球VHL社区受益，通过这次审查。
方法：TENGEN（法国神经内分泌肿瘤肿瘤遗传学网络）和PREDIR（法国国家癌症研究所肾癌遗传易感性网络）网络收集了所有VHL的VHL遗传变异和临床特征。法国进行VHL基因测试的9个实验室之一从2003年到2021年进行了分析。识别的变异在基因座特异性数据库中注册，通用变异数据库-VHL数据库(http://www.umd.是/VHL/）。
结果：在这里，我们报告了164个变体的专家分类，包括所有错义变体(n=124)，所有难以解释的变异(n=40)及其相关表型。在最初的美国医学遗传学学院分类之后，VHL专家组进行了第一轮分类,随后对不一致和模棱两可的病例进行了第二轮分类.总的来说,VHL专家修改了87种变异的分类,包括30种具有不确定意义的变异,其中19种(可能)为致病性变异,11种可能为良性变异.
结论：因此，这项工作允许对45个VHL疑似家庭进行诊断并影响了遗传咨询，并可以使全球VHL社区受益，通过这次审查。
