Professor Hartmut Neumann, a nephrologist at Albert-Ludwigs-University of Freiburg, Germany, is working on pedigrees of patients with the Black Forest mutation, which may be written

c. 505 T>C (Y98H) (old style) or
c.292T>C (p.Tyr98His) in standard nomenclature.

He is especially interested in patients with this mutation living outside of Germany. He knows that there are many people from this lineage in the USA, whose ancestors moved to Pennsylvania in the 1600’s from the Black Forest area of Germany. There may also be people from this lineage in South Africa, Australia, or other countries.

While most people with VHL are not related to one another and have many different kinds of changes in the VHL gene, this one large extended family was identified in 1995 by Dr. Neumann in Germany and Dr. Berton Zbar in the United States. Because they share a common mutation and have a fairly well-recorded family history, Neumann and Zbar were able to determine that VHL has existed in this lineage since before some members left for Pennsylvania in the 17th Century.

This phenomenon is called the Founder Effect -- we can identify a lineage where there is one Founder prior to the exodus of the Pennsylvania members of the family from Germany.

If you have this particular mutation type, he would like very much to be in touch with you. He is at the University of Freiburg in Germany, and serves on the medical advisory board of the VHL Family Alliance. If you are willing to share some information with him, please contact him directly at DrNeumann@vhl.org, or by mail at

                Dr. Hartmut Neumann
                University Medical Clinic
                Hugstetter Strasse 55
                Freiberg im Breisgau
                D-79106 Germany

Reference: Brauch et al, “Von Hippel-Lindau (VHL) disease with pheochromocytoma in the Black Forest region of Germany: evidence for a founder effect Human Genetics, 1995 May;95(5):551-6.

Abstract: We identified a germline missense mutation at nucleotide 505 (T to C) of the VHL tumor suppressor gene in 14, apparently unrelated, VHL type 2A families from the Black Forest region of Germany. This mutation was previously identified in two VHL 2A families living in Pennsylvania (USA). All affected individuals in the 16 families shared the same VHL haplotype indicating a founder effect. This missense mutation at codon 169 (Tyr to His) would probably cause an alteration in the structure of the putative VHL protein. The association of this distinct mutation with the pheochromocytoma phenotype in VHL may help to elucidate the genetic mechanism of carcinogenesis in this multi tumor cancer syndrome.

As printed in the VHL Family Forum 16:3, September 2008. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org.