Study on the germline FLCN mutations and the mechanism of pulmonary cyst formation in Birt-Hogg-Dube syndrome

为了了解BHD综合征肺囊肿形成的机制，我检测了BHDS患者的种系FLCN突变，并检测了BHDS患者分离的肺成纤维细胞的功能。我鉴定的种系FLCN突变分布在FLCN基因的所有外显子中，但在我们的日本BHDS患者中经常发现四种突变。基因型-表型相关性目前正在研究中。至于BHDS肺成纤维细胞的功能分析，我检查了增殖、迁移和凝胶收缩能力。与人胎肺成纤维细胞（HFL）相比，BHDS肺成纤维细胞向纤维连接蛋白的迁移减少，而增殖和凝胶收缩能力与HFL相似。实时荧光定量PCR检测BHDS肺成纤维细胞中TGF β 1、纤维连接蛋白、I型胶原蛋白表达降低。

In order to understand the mechanism of pulmonary cyst formation in Birt-Hogg-Dube(BHD) syndrome, I examined the germline FLCN mutation in patients with BHDS and functional assay of lung fibroblasts isolated from patients with BHDS. Germline FLCN mutations I identified distributed all exons of the FLCN gene, but four mutations were frequently demonstrated in our Japanese BHDS patients. Genotype-phenotype correlation is currently under investigation. As for functional analysis of BHDS lung fibroblasts, I examined proliferation and the ability of migration and gel contraction. As compared with human fetal lung fibroblasts(HFL), lung fibroblasts from BHDS showed decreased migration toward fibronectin while proliferation and gel contraction ability was similar to those with HFL. In addition, the expression of TGF beta 1, fibronectin, type I collagen was decreased in BHDS lung fibroblasts when determined by real-time PCR.