Germ-line mutations in nonsyndromic pheochromocytoma.

Background: The group of susceptibility genes for pheochromocytoma that included the proto-oncogene RET (associated with multiple endocrine neoplasia type 2 [MEN-2]) and the tumor-suppressor gene VHL (associated with von Hippel-Lindau disease) now also encompasses the newly identified genes for succinate dehydrogenase subunit D (SDHD) and succinate dehydrogenase subunit B (SDHB), which predispose carriers to pheochromocytomas and glomus tumors. We used molecular tools to classify a large cohort of patients with pheochromocytoma with respect to the presence or absence of mutations of one of these four genes and to investigate the relevance of genetic analyses to clinical practice.

Methods: Peripheral blood from unrelated, consenting registry patients with pheochromocytoma was tested for mutations of RET, VHL, SDHD, and SDHB.

Recurrent polytopic chromaffin paragangliomas in a 9-year-old boy resulting from a novel germline mutation in the von Hippel-Lindau gene.

Pheochromocytomas are frequently associated with inherited cancer syndromes such as von Hippel-Lindau disease (VHL). Retinal angioma and hemangioblastomas of the central nervous system are hallmarks of VHL, but its clinical variety is remarkably broad. Pheochromocytomas as the sole or first manifestation of VHL are rare but have been observed.

ATP release in human kidney cortex and its mitogenic effects in visceral glomerular epithelial cells.

Background: In chronic renal failure the sympathetic nervous system is activated. Sympathetic cotransmitters released within the kidney may contribute to the progression of renal disease through receptor-mediated proliferative mechanisms.

Methods: In human renal cortex electrical stimulation induced adenosine 5'-triphosphate (ATP; luciferin-luciferase-assay) and norepinephrine (HPLC) release was measured.