Comprehensive characterization of a Canadian cohort of von Hippel-Lindau disease patients.

Adolescent Adult Aged Aged, 80 and over Canada / epidemiology Central Nervous System / metabolism Child Child, Preschool Female Hemangioblastoma / epidemiology Humans Male Middle Aged Mutation, Missense / genetics Pedigree Penetrance Pheochromocytoma / epidemiology Von Hippel-Lindau Tumor Suppressor Protein / genetics Young Adult von Hippel-Lindau Disease / epidemiology

VHL clinical database hemangioblastoma neuroendocrine neoplasms pheochromocytoma renal cell carcinoma von Hippel-Lindau disease

Journal

Clinical genetics

ISSN: 1399-0004

Titre abrégé: Clin Genet

Pays: Denmark

ID NLM: 0253664

Informations de publication

Date de publication:
11 2019

Historique:

received: 11 04 2019

revised: 06 07 2019

accepted: 18 07 2019

pubmed: 2 8 2019

medline: 1 9 2020

entrez: 2 8 2019

Statut: ppublish

Résumé

Von Hippel-Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web-based application, REDCap, that thoroughly captures all VHL manifestation data. As an initial trial, information from 86 VHL patients from the University Health Network/Hospital for Sick Children was populated into the database. Analysis of this cohort showed missense variants occurring with the greatest frequency, with all variants localizing to the α- or β-domains of VHL. The most prevalent manifestations were central nervous system (CNS), renal, and retinal neoplasms, which were associated with frameshift variants and large deletions. We observed greater age-related penetrance for CNS hemangioblastomas with truncating variants compared to missense, while the reverse was true for pheochromocytomas. We demonstrate the utility of a comprehensive VHL database, which supports the standardized collection of clinical and genetic data specific to this patient population. Importantly, we expect that its web-based design will facilitate broader international collaboration and lead to a better understanding of VHL.

Identifiants

DOI: 10.1111/cge.13613 PMID: 31368132

pubmed: 31368132

doi: 10.1111/cge.13613

doi:

Substances chimiques

Von Hippel-Lindau Tumor Suppressor Protein EC 2.3.2.27

VHL protein, human EC 6.3.2.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

461-467

Informations de copyright

Références

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