Abstract 1848: Folliculin (FLCN) sequence variants involved in Birt-Hogg-Dube syndrome

Abstract

Abstract Background: Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominantly inherited familial cancer syndrome characterized 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 characterized but recent studies have suggested that it may be implicated in the regulation of several key signalling pathways including the AMPK-mTOR route. Methods: We previously established an online locus-specific database (LSDB) for FLCN sequence variants at www.lovd.nl/flcn. Variants in the database have been curated from the published literature and novel unpublished sequence variants submitted to the database from diagnostic and research laboratories working on BHD syndrome. The entries in the database were analyzed looking at the variant type and distribution and associated phenotype. Results: The database currently contains a total of 115 unique sequence variants (including 70 pathogenic, 7 probably pathogenic, 1 variant of unknown significance and 37 single nucleotide polymorphisms) in FLCN. The majority of pathogenic mutations results in protein truncation whilst a minority are splice-site alterations. An up to date summary of the variants and their associated phenotype will be presented. Conclusion: Pathogenic mutations are found throughout the coding regions (exons 4-14) and there are no apparent genotype-phenotype correlations. The FLCN mutation database available at www.lovd.nl/flcn offers a valuable resource and tool for clinicians involved in the management of BHD patients, clinical geneticists and researchers. Researchers can directly submit new sequence variants online to the database or by e-mailing the author. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1848.