Update of the UMD-VHL database: classification of 164 challenging variants based on genotype-phenotype correlation among 605 entries.

Autor:	Mougel G; Aix Marseille Univ, APHM, INSERM, MMG, U1251, GEnOPé Departement, M2GM, Timone Hospital, Marseille, France., Mohamed A; APHM, GEnOPé Department, M2GM, Timone Hospital, Marseille, France., Burnichon N; Département de Médecine Génomique des Tumeurs et des Cancers, Hôpital européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Inserm, PARCC, Paris, France., Giraud S; Genetics Department, Hospices Civils de Lyon (HCL), University Hospital, East Pathology Center, Lyon, France., Pigny P; Service de Biochimie et Biologie Moléculaire « Hormonologie, Métabolisme-Nutrition, Oncologie », Centre de Biologie Pathologie, CHU Lille, Bd du Pr J Leclercq, Lille, France., Bressac-de Paillerets B; Service de Genetique, Département de Biologie et Pathologies Médicales, Gustave Roussy; INSERM U1279, Université Paris-Saclay, Villejuif Cedex, France., Mirebeau-Prunier D; Département de Biochimie et Génétique, Service de Biochimie et Biologie Moléculaire, CHU d'Angers, University of Angers, INSERM, CNRS, MITOVASC, Equipe MitoLab, SFRICAT, Angers, France., Buffet A; Département de Médecine Génomique des Tumeurs et des Cancers, Hôpital européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Inserm, PARCC, Paris, France., Savagner F; Laboratoire de Biochimie, Institut Fédératif de Biologie, CHU Toulouse; Inserm UMR1297, I2MC, Toulouse, France., Romanet P; Aix Marseille Univ, APHM, INSERM, MMG, U1251, GEnOPé Departement, M2GM, Timone Hospital, Marseille, France., Arlot Y; CNRS UMR6290, Université Rennes 1, SFR-UMS CNRS 3480, INSERM 018, Rennes, France., Gardie B; Ecole Pratique des Hautes Etudes, EPHE, Université PSL; Université de Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France., Gimenez-Roqueplo AP; Département de Médecine Génomique des Tumeurs et des Cancers, Hôpital européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Inserm, PARCC, Paris, France., Beroud C; Department of Genetics, M2GM, Timone Hospital, Aix Marseille Univ, APHM, INSERM, MMG, U1251 Bioinformatic Team, Marseille, France., Richard S; Ecole Pratique des Hautes Etudes, EPHE, Université PSL, France, UMR 9019-CNRS, Gustave Roussy Cancer Campus, Villejuif, France et Service d'Urologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France.; Réseau National pour Cancers rares de l'Adulte PREDIR labellisé par l'INCa, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Paris, France., Barlier A; Aix Marseille Univ, APHM, INSERM, MMG, U1251, GEnOPé Departement, M2GM, Timone Hospital, Marseille, France anne.barlier@univ-amu.fr.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2024 Mar 21; Vol. 61 (4), pp. 378-384. Date of Electronic Publication: 2024 Mar 21.
DOI:	10.1136/jmg-2023-109550
Abstrakt:	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. 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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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