Familial Pheochromocytoma Due to Mutant von Hippel-Lindau Disease Gene

The subtitle of our last clinical report,¹which is now a 37-year follow-up of a large western Pennsylvania kindred with 16 members with pheochromocytoma,²hinted that a mutation in the von Hippel-Lindau (VHL) disease gene may have been present. We so speculated because 3 relatives with pheochromocytoma and 3 without it had other manifestations of VHL disease. Using 2 different molecular methods, we have now demonstrated a germline mutation in theVHLgene on chromosome 3 in the family. As reported elsewhere in detail,³genomic DNA was amplified in our laboratory in Frederick, Md, using the polymerase chain reaction, with primers and conditions as previously published.⁴The results of single-strand conformational polymorphism analysis indicated an abnormal conformer, and direct sequencing of the mutant conformer demonstrated a T to C transversion at nucleotide 547 of theVHLcomplementary DNA,^4,5resulting in a tyrosine to histidine missense