Liu Yaping, Xu Zhiyan, Feng Ruie, Zhan Yongzhong, Wang Jun, Li Guozhen, Li Xue, Zhang Weihong, Hu Xiaowen, Tian Xinlun, Xu Kai-Feng, Zhang Xue
McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
Department of Internal Medicine, Peking Union Medical College Hospital, Beijing, China.
Orphanet J Rare Dis. 2017 May 30;12(1):104. doi: 10.1186/s13023-017-0656-7.
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder, the main manifestations of which are fibrofolliculomas, renal tumors, pulmonary cysts and recurrent pneumothorax. The known causative gene for BHD syndrome is the folliculin (FLCN) gene on chromosome 17p11.2. Studies of the FLCN mutation for BHD syndrome are less prevalent in Chinese populations than in Caucasian populations. Our study aims to investigate the genotype spectrum in a group of Chinese patients with BHD.
We enrolled 51 patients with symptoms highly suggestive of BHD from January 2014 to February 2017. The FLCN gene was examined using PCR and Sanger sequencing in every patient, for those whose Sanger sequencing showed negative mutation results, multiplex ligation-dependent probe amplification (MLPA) testing was conducted to detect any losses of large segments.
Among the 51 patients, 27 had FLCN germline mutations. In total, 20 mutations were identified: 14 were novel mutations, including 3 splice acceptor site mutations, 2 different deletions, 6 nonsense mutations, 1 missense mutation, 1 small insertion, and 1 deletion of the whole exon 8.
We found a similar genotype spectrum but different mutant loci in Chinese patients with BHD compared with European and American patients, thus providing stronger evidence for the clinical molecular diagnosis of BHD in China. It suggests that mutation analysis of the FLCN gene should be systematically conducted in patients with cystic lung diseases.
Birt-Hogg-Dubé综合征（BHD）是一种常染色体显性疾病，其主要表现为纤维毛囊瘤、肾肿瘤、肺囊肿和复发性气胸。已知的BHD综合征致病基因是位于17号染色体p11.2上的卵泡抑素（FLCN）基因。在中国人群中，关于BHD综合征的FLCN突变研究不如在白种人群中普遍。我们的研究旨在调查一组中国BHD患者的基因型谱。
我们纳入了2014年1月至2017年2月期间51例症状高度疑似BHD的患者。对每位患者使用聚合酶链反应（PCR）和桑格测序法检测FLCN基因，对于桑格测序显示无突变结果的患者，进行多重连接依赖探针扩增（MLPA）检测以检测大片段缺失。
51例患者中，27例存在FLCN种系突变。共鉴定出20种突变：14种为新突变，包括3种剪接受体位点突变、2种不同的缺失、6种无义突变、1种错义突变、1种小插入和1种外显子8的整体缺失。
我们发现中国BHD患者的基因型谱与欧美患者相似，但突变位点不同，从而为中国BHD的临床分子诊断提供了更有力的证据。这表明对于患有囊性肺疾病的患者，应系统地进行FLCN基因的突变分析。
