A31
The Folliculin (FLCN) mutation database: an online resource for FLCN sequence variants involved in Birt-Hogg-Dube syndrome
Derek Lim1, Pauline Rehal2, Fiona MacDonald2, Eamonn Maher1
1University of Birmingham, UK, 2West Midlands Regional Genetics Service, Birmingham, UK
Background
Birt-Hogg-Dub (BHD) syndrome is an autosomal dominantly inherited familial cancer syndrome characterised most commonly by the development of facial fibrofolliculomas, pulmonary cysts (predisposing to spontaneous pneumothorax) and renal cancer. Germline mutations in FLCN on 17p11.2 have been reported in patients with BHD and also in patients with isolated familial primary spontaneous pneumothorax and familial clear cell renal cell carcinoma without other features of BHD. The function of the FLCN gene product, folliculin, is not well characterised but recent studies have suggested that it may be implicated in the regulation of several key signalling pathways including the AMPK-mTOR route.
Method
We have set up an online locus-specific database (LSDB) for FLCN sequence variants using the Leiden Open (source) Variant Database (LOVD) software. To date the variants described in the database were extracted from the published literature and from unpublished mutations detected in our centre.
Results
The database currently contains a total of 68 unique variants (64 pathogenic, 3 probably pathogenic and 1 variant of unknown significance) including 9 novel variants from our centre. The number of unique variants will continue to expand as unpublished novel variants from our European collaborators and SNP data is added.
Conclusion
We describe the FLCN mutation database available at www.lovd.nl/flcn . The database offers a valuable resource and tool for clinicians involved in the management of BHD patients, clinical geneticists and researchers, and will aid genotype-phenotype correlations studies. Researchers can directly submit new sequence variants online to the database or by e-mailing the author.
