Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant cancer syndrome caused by a germline mutation of the folliculin (FLCN) gene. Previous studies have suggested that truncated mutant folliculin proteins generated by disease causing FLCN mutations may retain partial functionality and contribute to disease phenotype. A 38-year-old Russian man presented with a left renal tumor. He underwent a left radical nephrectomy and histological examination confirmed the diagnosis of chromophobe renal cell carcinoma. He had papulae on his face suggestive of fibrofolliculomas, and pulmonary cysts on his computed tomography of the chest. He had a family history of skin manifestations. Genetic analysis identified a genomic deletion including the putative promoter region of FLCN exon 1 in the germline, and the second hit on the remaining wild-type FLCN in the renal carcinoma cells, which is expected to cause the complete lack of folliculin protein. Immunohistochemistry with the use of anti-folliculin antibody showed no antibody-binding on chromophobe renal carcinoma cells. These findings suggest that the decreased FLCN expression itself without producing mutated folliculin proteins can be at risk for developing clinical manifestations of BHDS: fibrofolliculomas, lung cysts, and tumorigenesis in the kidneys. This sheds light on the pathogenesis of BHDS and the role of FLCN as a tumor suppressor gene.

Birt-Hogg-Dubé综合征（BHDS）是由卵泡蛋白（FLCN）基因的种系突变引起的常染色体显性癌症综合征。以前的研究表明，由引起FLCN突变的疾病产生的截短的突变卵泡蛋白可能保留部分功能并有助于疾病表型。一名38岁的俄罗斯男子患有左肾肿瘤。他接受了左根肾切除术，组织学检查证实了发色肾细胞癌的诊断。他的脸上有丘疹，提示有纤维滤泡瘤，胸部计算机断层扫描显示有肺囊肿。他有皮肤病的家族史。遗传分析确定了一个基因组缺失，包括FLCN的推定启动子区域生殖细胞外显子1，第二次击中肾癌细胞中剩余的野生型FLCN，这有望导致卵泡蛋白完全缺乏。使用抗滤泡蛋白抗体的免疫组织化学显示，在发色肾癌细胞上没有抗体结合。这些发现表明，FLCN表达本身下降而不产生突变的卵泡蛋白可能会威胁到BHDS的临床表现：纤维滤泡瘤，肺囊肿和肾脏中的肿瘤发生。这揭示了BHDS的发病机理以及FLCN作为抑癌基因的作用。