Abstract

Rationale: Birt-Hogg-Dube (BHD) syndrome, a rare inherited autosomal genodermatosis first recognized in 1977, is characterized by fibrofolliculomas of the skin, an increased risk of renal tumors, and multiple lung cysts with spontaneous pneumothorax. The BHD gene, a tumor suppressor gene located in chromosome 17p11.2, has recently been identified to be defective. Recent genetic studies revealed that clinical pictures of the disease may be variable and may not always demonstrate the full expression of phenotypes.

Objectives: We hypothesized that mutations of the BHD gene are responsible for patients who have multiple pulmonary cysts of which the underlying causes have not yet been elucidated.

Methods: We studied 8 patients with pulmonary cysts, without skin and renal diseases; 7 patients have past histories of spontaneous pneumothorax, and 5 patients have family histories of pneumothorax. The BHD gene was examined with polymerase chain reaction, denaturing high-performance liquid chromatography and direct sequencing.

Main Results: We found that 5 of 8 patients had BHD germline mutation. All mutations were unique and 4 of them were novel, including 3 different deletions or insertions detected in exon 6, 12, and 13, respectively, and one splice acceptor site mutation in intron 5 resulting in in-frame deletion of exon 6.

Conclusions: We demonstrated that germline mutations of the BHD gene are involved in some patients with multiple lung cysts and pneumothorax. Pulmonologists should be aware of BHD syndrome since it can occur as an isolated phenotype with pulmonary involvement.