Molecular diagnosis of von Hippel-Lindau disease in a kindred with a predominance of familial phaeochromocytoma.

OBJECTIVE: To study the presence of germline mutations in the von Hippel-Lindau gene (vhl) in a kindred with a predominance of familial phaeochromocytoma in order to confirm the diagnosis of von Hippel-Lindau disease (VHLD) as well as to identify asymptomatic members.
DESIGN: DNA extracted from peripheral blood was amplified by the polymerase chain reaction using oligonucleotide primers corresponding to exon 3 of the vhl gene. Specific mutations in codon 238 were screened by restriction endonuclease digestion of PCR products with Msp I. The results were confirmed by DNA sequence analysis. PATIENTS: Two generations of a family consisting of 15 individuals were studied.
RESULTS: A germline missense point mutation at codon 238 of the vhl gene (CGG-->TGG; Arg-->Trp) was 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 specific diagnosis of von Hippel-Lindau disease, and is a good method for the identification of asymptomatic individuals at risk of von Hippel-Lindau disease.