Question: I am doing an oral report on VHL for a genetics class. What is the specific mutation rate for the VHL gene? I realize that the prevalence is about one in 36,000, but for tumors to occur, both genes must become inactive. Is there a published rate for the mutation of the VHL gene?

-- David V.

Answer: According to our paper in 1991 the new mutation rate in VHL is similar to that in retinoblastoma. Genetic aspects of von Hippel-Lindau (VHL) disease were studied in familial and isolated cases. Complex segregation analysis with pointers was performed in 38 kindreds with two or more affected members. Dominant inheritance with almost complete penetrance in the highest age classes (0.96 at 51 to 60 and 0.99 at 61 to 70 years) was confirmed and there was no evidence of heterogeneity between families ascertained through complete and incomplete selection. The point prevalence of heterozygotes in East Anglia, England, was 1.89/100,000 (1/53,000) persons with an estimated birth incidence of 2.73/100,000 (1/36,000) live births. Reproductive fitness was 0.83. Direct and indirect estimates of the mutation rate were 4.4 (95% CI 0.9 to 7.9) x 10(-6)/gene/generation and 2.32 x 10(-6)/gene/generation respectively. There was no significant association between parental age or birth order and new mutations for VHL disease.

-- Eamonn R. Maher, Professor of Genetics, University of Birmingham, England.

ER Maher, L Iselius, JR Yates, M Littler, C Benjamin, R Harris, J Sampson, A Williams, MA Ferguson-Smith and N Morton Cambridge University, Department of Pathology, "Von Hippel-Lindau disease: a genetic study." Journal of Medical Genetics 28 (1991) 443-447.

As printed in the VHL Family Forum 8:2, June 2000. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.