Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database.

Fibrillin is the major component of extracellular microfibrils. Mutations in the fibrillin gene on chromosome 15 (FBN1) were first described in the heritable connective disorder, Marfan syndrome (MFS). FBN1 has also been shown to harbor mutations related to a spectrum of conditions phenotypically related to MFS, called "type-1 fibrillinopathies." In 1995, in an effort to standardize the information regarding these mutations and to facilitate their mutational analysis and identification of structure/function and phenotype/genotype relationships, we created a human FBN1 mutation database, UMD-FBN1. This database gives access to a software package that provides specific routines and optimized multicriteria research and sorting tools. For each mutation, information is provided at the gene, protein, and clinical levels. This tool is now a worldwide reference and is frequently used by teams working in the field; more than 220,000 interrogations have been made to it since January 1998. The database has recently been modified to follow the guidelines on mutation databases of the HUGO Mutation Database Initiative (MDI) and the Human Genome Variation Society (HGVS), including their approved mutation nomenclature. The current update shows 559 entries, of which 421 are novel. UMD-FBN1 is accessible at www.umd.be/. We have also recently developed a FBN1 polymorphism database in order to facilitate diagnostics.

Absence of exon 15 BRAF germline mutations in familial melanoma.

We have analyzed DNA from peripheral blood of 42 cases of familial melanoma for germline mutations in exon 15 of the BRAF gene. No evidence of mutation was found. We have also analyzed DNA extracted from secondary melanoma from two members of these families. These results were also negative. In addition we have searched for exon 15 BRAF mutations in 24 samples of secondary melanoma from 22 cases of sporadic melanoma and detected the 1796T>A BRAF mutation which leads to a substitution of valine by glutamic acid at position 599 (V599E) in six samples. Peripheral blood DNA from two of these tumor-positive cases of sporadic melanoma were negative for the V599E BRAF mutation. This mutation therefore appears to be a somatic mutation associated with melanoma development and/or progression in a proportion of affected individuals.