MOLECULAR DIAGNOSIS OF VON-HIPPEL-LINDAU-DISEASE IN A KINDRED WITH A PREDOMINANCE OF FAMILIAL PHEOCHROMOCYTOMA

OBJECTIVE To study the presence of germline mutations in the von Hippe l-Lindau gene (vhl) in a kindred with a predominance of familial phaeo chromocytoma in order to confirm the diagnosis of von Hippel-Lindau di sease (VHLD) as well as to identify asymptomatic members. DESIGN DNA e xtracted from peripheral blood was amplified by the polymerase chain r eaction using oligonucleotide primers corresponding to exon 3 of the v hl gene. Specific mutations in codon 238 were screened by restriction endonuclease digestion of PCR products with Msp I. The results were co nfirmed by DNA sequence analysis. PATIENTS Two generations of a family consisting of 15 individuals were studied. RESULTS A germline missens e point mutation at codon 238 of the vhl gene (CGG-->TGG; Arg-->Trp) w as detected in all patients with phaeochromocytoma and in only one of the asymptomatic family members. CONCLUSION Mutational analysis of the vhl gene in patients with familial phaeochromocytoma may permit speci fic diagnosis of von Hippel-Lindau disease, and is a good method for t he identification of asymptomatic individuals at risk of von Hippel-Li ndau disease.