There are now 502 different mutations registered in the Worldwide VHL Mutations Database, maintained at the Arnaud de Villeneuve Hospital in Montpellier, France, by Assistant Prof. Christophe Béroud. Each one represents a unique family strain. If two or more families have exactly the same mutation type, they would be seen only once in this database. Thus all the member families in the Black Forest Family in Germany and Pennsylvania count as one.

There are a total of 912 mutations registered in the database. Four hundred and seventy three were collected from VHL families, 388 from sporadic tumors and 51 from cell lines. Only few of these mutations were reported multiple time and so far 502 different mutations have been reported for the VHL gene.

The accompanying illustration shows the distribution of the overall mutations along the gene. In blue (the lower scale, marked "mRNA") are the three exons of the gene, with the scale marked in nucleotides. In yellow and green (the wider band marked "NH2"), depicts the different regions of the protein with the scale marked in amino acids. At the bottom are the number of mutations in each position. Dr. Christophe Béroud and his research group at the Arnaud de Villenueve Hospital in Montpellier, France, established the Universal Mutation Database on the internet, including the Universal VHL-Mutation Database, at http://www.umd.be/

This database is mainly useful for research but can be accessed by any researcher, geneticist or clinician. This is a new kind of database which includes a software utility to query the database online. You also have access to numerous dedicated analysis tools and a graphical display.

The initial nucleotide numbering scheme (with 505 and 712 mutations) was based on the initial cloning of the VHL gene which did not precisely describe the start and stop markers of the gene. A new numbering system was introduced in the late ‘90’s, where the first amino acid of VHL is number 1. If you know the older number, subtract 213 to arrive at the new nucleotide number, or subtract 71 to arrive at the new amino acid number. It takes three nucleotides to make one amino acid, so there are three times as many nucleotides as amino acids.

For example, the Black Forest mutation (505 in the old nomenclature) is now nucleotide 292 corresponding to AA 98 (292 divided by 3). 712 (old nomenclature) is now nucleotide 499 or AA 167 (499 divided by 3).

This database is developed at the Molecular Biology Laboratory directed by Prof. Mireille Claustres. Dr Béroud and his research group designed it to assist researchers in identifying the functional parts of the gene, and helping to understand the function of the gene and its protein. Ultimately, this tool should help to establish genotype-phenotype correlation.

Researchers who use the database are asked to acknowledge in their publications the Universal Mutation Database references listed on the website. Submission of new mutations to the database can be made by E-mail to Christophe.Beroud@igh.cnrs.fr

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As printed in the VHL Family Forum 12:2, August/September 2004, with updated provided by Dr. Béroud 10 September 2004. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org.