Birt-Hogg-Dubé (BHD) syndrome: report of two novel germline mutations in the folliculin (FLCN) gene.

Molecular analysis of the folliculin (FLCN) gene was performed in four consenting patients from two families with Birt-Hogg-Dubé (BHD) syndrome, showing the occurrence of two frameshift mutations located respectively in exons 5 (802insA) and 9 (1345delAAAG) of the FLCN gene. A novel homozygous sequence variant in the intron 9 (IVS9 +5C>T) was also found. 1345delAAAG was associated with a wide variety of tumors, including stomach, colon, breast and parotid cancer. Conversely, the family carrying 802insA only had clinical evidence of dermatological lesions. These findings further suggest the relevance of exon 9 mutations in cancer predisposition for BHD.