Mutations of the Birt-Hogg-Dube gene in patients with multiple lung cysts and recurrent pneumothorax
Mutations of the Birt-Hogg-Dube gene in patients with multiple lung cysts and recurrent pneumothorax
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DOI：
10.1136/jmg.2007.049874
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发表时间：
2007-09-01
影响因子：
4
通讯作者：
Seyama, Kuniaki
中科院分区：
文献类型：
--
作者：
Gunji, Yoko;Akiyoshi, Taeko;Seyama, Kuniaki
理由：Birt-Hogg-Dube (BHD) 综合征是一种罕见的常染色体遗传性皮肤病，于 1977 年首次被发现，其特征是皮肤纤维毛囊瘤、肾肿瘤和多发性肺囊肿伴自发性气胸的风险增加。 BHD 基因是一种位于染色体 17p11.2 的抑癌基因，最近被证明存在缺陷。最近的遗传学研究表明，该疾病的临床表现可能有所不同，并且可能并不总是呈现表型的完整表达。 目的：我们假设 BHD 基因突变是导致患有多发性肺囊肿的患者的原因，其根本原因尚未阐明。 方法：我们研究了 8 名没有皮肤和肾脏疾病的肺囊肿患者；其中七名患者有自发性气胸病史，五名患者有气胸家族史。使用PCR、变性高效液相色谱和直接测序来检查BHD基因。主要结果：我们发现8名患者中有5名患有BHD种系突变。所有突变都是独特的，其中四种是新的，包括分别在外显子 6、12 和 13 中检测到的三种不同的缺失或插入，以及内含子 5 中的一个剪接受体位点突变导致外显子 6 的框内缺失。结论：我们发现 BHD 基因的种系突变与一些多发性肺囊肿和气胸患者有关。肺科医生应该意识到，BHD 综合征可以作为一种孤立的肺部受累表型发生。
Rationale: Birt-Hogg-Dube (BHD) syndrome, a rare inherited autosomal genodermatosis first recognised in 1977, is characterised by fibrofolliculomas of the skin, an increased risk of renal tumours and multiple lung cysts with spontaneous pneumothorax. The BHD gene, a tumour suppressor gene located at chromosome 17p11.2, has recently been shown to be defective. Recent genetic studies revealed that clinical pictures of the disease may be variable and may not always present the full expression of the phenotypes.Objectives: We hypothesised that mutations of the BHD gene are responsible for patients who have multiple lung cysts of which the underlying causes have not yet been elucidated.Methods: We studied eight patients with lung cysts, without skin and renal disease; seven of these patients have a history of spontaneous pneumothorax and five have a family history of pneumothorax. The BHD gene was examined using PCR, denaturing high- performance liquid chromatography and direct sequencing.Main results: We found that five of the eight patients had a BHD germline mutation. All mutations were unique and four of them were novel, including three different deletions or insertions detected in exons 6, 12 and 13, respectively and one splice acceptor site mutation in intron 5 resulting in an inframe deletion of exon 6.Conclusions: We found that germline mutations of the BHD gene are involved in some patients with multiple lung cysts and pneumothorax. Pulmonologists should be aware that BHD syndrome can occur as an isolated phenotype with pulmonary involvement.