Genetic investigation and genotype-phenotype correlation in the von-Hippel Lindau disease

• Grant number: 23/02222-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2023
• Effective date (End): February 29, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Madson Queiroz Almeida
• Grantee: Gustavo Henrique Mori
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 19/15873-6 - Investigation of new genetic, clinical and pathological aspects of endocrine arterial hypertension, AP.TEM

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia, respectively. PPGLs have the highest degree of heritability among endocrine tumors. Currently, ~40% of individuals with PPGLs have a genetic germline and there are at least 12 different genetic syndromes related to these tumors, such as multiple endocrine neoplasia 2, von-Hippel Lindau disease (VHL) e neurofibromatose 1. VHL is an autosomal dominant, inherited tumor predisposition syndrome caused by germline mutations in the VHL tumor suppressor gene. VHL diagnosis is established in an individual with a single characteristic VHL-related tumor (i.e., CNS or retinal hemangioblastoma, renal cell carcinoma, PPGL or pancreatic neuroendocrine tumor) and a family history of VHL. Approximately 50% of VHL patients develop PPGLs, mainly pheochromocytomas (60% bilateral). We have actually approximately 50 patients with VHL. Our aims in this project is to investigate de genetic etiology of patients with clinical diagnosis of VHL and in their first-degree relatives. Moreover, the genotype-phenotype correlation will be investigated in the VHL cohort.