نبذة مختصرة : International audience ; 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 locusspecific 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. Conclusion 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. ; La maladie de von Hippel-Lindau (VHL) est un syndrome tumoral héréditaire causé par des mutations germinales du gène suppresseur de tumeur VHL. L'identification des variants VHL nécessite une classification précise qui a un impact sur la prise en charge des patients et le conseil génétique. Méthodes: Les réseaux TENGEN (Réseau français d'oncogénétique des tumeurs neuroendocrines) et PREDIR (Réseau de prédispositions héréditaires au cancer du rein de ...
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