“Pheochromocytoma”, Victor McKusick, Mendelian Inheritance in Man, 1966. 嗜铬细胞瘤。(VHL).

Here I present: Pheochromocytoma”, Victor McKusick, Mendelian Inheritance in Man’, 1966. 嗜铬细胞瘤。(VHL).

INTRODUCTION.

Pheochromocytoma is tumor of the adrenal medulla composed of chromaffin cells and is part of the paraganglioma (PGL) family of tumors, being defined as an intra-adrenal PGL.  These neuroendocrine tumors can be sympathetic, where they release catecholamines into the bloodstream which cause the most common symptoms, including hypertension (high blood pressure), tachycardia (fast heart rate), sweating, and headaches.

Pheochromocytomas most commonly occur as part of  syndromes, and mutations in the genes that cause these syndromes have been identified in patients who manifest only pheochromocytoma. These syndromes include Von Hippel-Lindau syndrome, which is caused by a mutation in the VHL gene.

Von Hippel–Lindau tumor suppressor  is a protein that, in humans, is encoded by the VHL gene. Mutations of the VHL gene are associated with Von Hippel–Lindau disease, which is characterized by hemangioblastomas of the brain, spinal cord and retina. It is also associated with kidney and pancreatic lesions. Also, the protein product of the VHL gene play a role in the oxygen-sensing pathway, in microtubule stability and orientation, tumor suppression, cilia formation, regulation of senescence, cytokine signaling, collagen IV regulation, and assembly of a normal extracellular fibronectin matrix.

There is evidence that  susceptibility to the development of isolated pheochromocytoma can be caused by germline mutation in several genes, including the VHL gene on cytogenetic location 3p25.3 and genomic coordinates 3:10,141,778-10,153,667.  The screenshot of the VHL gene 11,890 bp (base pairs) of DNA sequence length is shown BELOW.  Nine  (9) other genes besides VHL in the 3p25.3 cytogenetic location are listed BENEATH.