Department of Dermatology and Allergology, University Hospital, LMU Munich, Munich, Germany.
Institute of Human Genetics, University Hospital, LMU Munich, Munich, Germany.
PLoS One. 2018 Dec 26;13(12):e0209504. doi: 10.1371/journal.pone.0209504. eCollection 2018.
Birt-Hogg-Dubé syndrome (BHDS) is a genetic tumor syndrome characterized by lung cysts, pneumothorax, fibrofolliculomas and renal cell cancer. The diagnosis of BHDS is usually considered if kidney cancer occurs before age 50 years, is multifocal and/or bilateral or of the oncocytoma/hybrid oncocytoma-chromophobe type. Using a sample of 50 BHDS families with a total of 178 patients we analyzed how many kidney cancer patients fulfilled one or more of these criteria. Furthermore, we addressed the question if genotype-phenotype-correlations exist that can be used for risk stratification. Renal cell cancer occurred in 34/178 (19.1%) patients, and the reported male bias was not observed. Furthermore, most kidney malignancies occurred after the age of 50 years. Thus, the majority of tumors did not show the typical hallmarks of BHDS. A below-average tumor frequency (17.2%) was observed for the known mutational hotspot c.1285delC/dupC that was the cause of BHDS in 24% of families. Unexpected was the high tumor frequency (66.7%) associated with mutation c.887C>G within a single family, a finding that merits further exploration.
Birt-Hogg-Dubé 综合征（BHDS）是一种遗传性肿瘤综合征，其特征为肺囊肿、气胸、毛囊瘤和肾细胞癌。如果肾癌发生在 50 岁之前、为多灶性和/或双侧性、或为嗜酸细胞瘤/混合嗜酸细胞瘤-嫌色细胞癌型，则通常考虑 BHDS 的诊断。我们使用 50 个 BHDS 家系的样本（共 178 例患者）进行分析，以确定有多少肾癌患者符合这些标准中的一项或多项。此外，我们还探讨了是否存在可用于风险分层的基因型-表型相关性。在 178 例患者中，有 34 例（19.1%）发生了肾细胞癌，并未观察到报告中的男性偏倚。此外，大多数肾癌发生在 50 岁以后。因此，大多数肿瘤未显示 BHDS 的典型特征。在已知的突变热点 c.1285delC/dupC 中，观察到低于平均水平的肿瘤频率（17.2%），该突变热点是 24%家系中 BHDS 的病因。出乎意料的是，在一个家系中发现突变 c.887C>G 与高肿瘤频率（66.7%）相关，这一发现值得进一步探索。
