The major genetic alterations involve RET (rearranged during transfection) is the causative gene underlying multiple endocrine neoplasia (MEN) type 2A and 2B that are more often associated with pheochromocytomas), VHL that causes von Hippel–Lindau disease, NF1 associated with neurofibromatosis type 1, and the SDHB, SDHD, and SDHC genes encoding subunits B, D, and C of the succinate dehydrogenase enzyme complex involved in the Krebs cycle. The gene discussed is NF1; the disease is von Hippel-Lindau disease.