Abstract
Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem neoplastic syndrome stemming from germline disease-associated variants of the VHL tumor suppressor gene on chromosome 3. VHL is involved, through the EPO-VHL-HIF signaling axis, in oxygen sensing and adaptive response to hypoxia, as well as in numerous HIF-independent pathways. The diverse roles of VHL confirm its implication in several crucial cellular processes. VHL variations have been associated with the development of VHL disease and erythrocytosis. The association between genotypes and phenotypes still remains ambiguous for the majority of mutations. It appears that there is a distinction between erythrocytosis-causing VHL variations and VHL variations causing VHL disease with tumor development. Understanding the pathogenic effects of VHL variants might better predict the prognosis and optimize management of the patient.
Highlights
Von Hippel-Lindau disease (VHL disease or von Hippel-Lindau tumor suppressor gene (VHL) syndrome) is a familial multisystem syndrome stemming from germline disease-associated variants of the VHL tumor suppressor gene on chromosome 3 [1]
Hereditary genetic changes in the VHL gene that result in the development of different tumors and erythrocytosis show great complexity, and present a significant challenge with regard to the elucidation of variants association with phenotypes
Recent research has revealed the involvement of VHL in different cellular processes and molecular pathways, both HIF-dependent and HIF-independent, as well as its ability to interact with many different proteins
Summary
Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem syndrome stemming from germline disease-associated variants of the VHL tumor suppressor gene on chromosome 3 [1]. It is an autosomal dominant neoplastic disorder in which multiple benign and malignant tumors, as well as cysts, develop in the central nervous system (the brain, spinal cord, retina, and inner ear) and visceral organs (kidney, adrenal gland, pancreas, epididymis, and broad ligament) [2,3]. The aim of this review is to provide an overview of the role of VHL gene mutations leading to the development of VHL disease and erythrocytosis, and to present a case of a patient with VHL disease due to a de novo mutation, to illustrate the role of genetic testing in the management of patients with genetic disease
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