Birt-Hogg-Dubé syndrome was described for the first time in 1997. The characteristic feature is the occurrence of multiple small lesions on the face, neck and the upper part of the trunk. These lesions are characterized as fibrofoliculomas and trichodiscomas. Birt-Hogg-Dubé syndrome is also rarely associated with renal tumors, spontaneous pneumothorax, intestinal adenomas and carcinomas.

The disease has autosomal dominant inheritence. In 2002, at the locus 17p11.2 the gene BHD was identified whose mutations are the cause of Birt-Hogg-Dubé syndrome. It concerns mostly deletions, insertions or nonsense mutations causing shortening and loss of function of the BHD protein. In exon 11 there is a "hot-spot“ site consisting of eight cytosines in a row and the majority of the mutations, as single base insertions or deletions, are located heree.


We investigate all fourteen coding exons of the BHD gene. We use PCR amplification of the targeted region and direct sequencing.

  • Slideshow Format

    Mutation of the BHD gene. Frameshift mutation c.1733insC.

Clinical sensitivity:

Germline mutations detected by sequence analysis of coding exons and exon-intron connections of the gene BHD (FLCN) are detected in approximately 88% of patients meeting the diagnostic criteria of Birte Hogge Dube' syndrome (Toro, 2008).

MLPA (Multiple-Ligation Probe Amplification) analysis of the mutation in a large-scale (amplification / deletion) detects about 3% of mutations in the gene BHD listed in a publicly available version of the mutation database HGMD.

Analytical sensitivity and specificity of the sequencing: 99%.


Mutations deep in the introns and regulatory sequences are not detected. Rare polymorphisms in the location of primers annealing may cause a diagnostic error.

In the case of analysis of somatic mutations sequencing mutations will not be detected, if the altered cell line is not represented by at least 20%.


  1. Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. Cancer Cell. 2002 Aug;2(2):157-64.
  2. Adley BP, Smith ND, Nayar R, Yang XJ. Birt-Hogg-Dubé syndrome: clinicopathologic findings and genetic alterations. Arch Pathol Lab Med. 2006 Dec;130(12):1865-70.