Comprehensive characterization of a Canadian cohort of von Hippel‐Lindau disease patients
| Autor: | Shereen Ezzat, Wei Xu, Normand Laperriere, Saleh Albanyan, Garrett Bullivant, Zsuzanna Lichner, Payal Jani, Andreea Chiorean, Gelareh Zadeh, Rachel H. Giles, Fady Hannah-Shmouni, Marta Szybowska, Lior Krimus, Marisa Sit, Yasser Salama, Yuvreet Kaur, Chansonette Badduke, Nathan F. Schachter, Michael A.S. Jewett, Raymond H. Kim, Hatem Krema, David Malkin, Tracy Stockley, Ozgur Mete, Karen Gomez Hernandez, Sylvia L. Asa, Cara Inglese, Harriet Druker, Bailey Gallinger, Jonathan D. Wasserman |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Central Nervous System Male 0301 basic medicine Oncology Canada medicine.medical_specialty von Hippel-Lindau Disease Retinal Neoplasm Adolescent endocrine system diseases Mutation Missense Penetrance Pheochromocytoma Disease 030105 genetics & heredity urologic and male genital diseases Frameshift mutation Young Adult 03 medical and health sciences Hemangioblastoma Internal medicine Genetics medicine Humans Missense mutation Von Hippel–Lindau disease Child neoplasms Genetics (clinical) Aged Aged 80 and over business.industry Middle Aged medicine.disease female genital diseases and pregnancy complications Pedigree 030104 developmental biology Von Hippel-Lindau Tumor Suppressor Protein Child Preschool Female business |
| Zdroj: | Clinical Genetics. 96:461-467 |
| ISSN: | 1399-0004 0009-9163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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