Ren H-Z, Zhu C-C, Yang C, Chen S-L, Xie J, Hou Y-Y, Xu Z-F, Wang D-J, Mu D-K, Ma D-H, Wang Y, Ye M-H, Ye Z-R, Chen B-F, Wang C-G, Lin J, Qiao D, Yi L
Department of Pathology, Nanjing University Medical School, Nanjing, Jiangsu, China.
Clin Genet. 2008 Aug;74(2):178-83. doi: 10.1111/j.1399-0004.2008.01030.x. Epub 2008 May 25.
Primary spontaneous pneumothorax (PSP) is a common manifestation of Birt-Hogg-Dubé syndrome caused by folliculin gene (FLCN) mutation, which is also found in isolated familial PSP cases. A complete genetic analysis of FLCN was performed in 102 unrelated Chinese patients with isolated PSP and 21 of their family members. Three novel mutations (c.924_926del, c.1611_1631del and c.1740C>T) and a previously reported mutation (c.1733insC) were identified in five familial and five sporadic PSP patients. Of the 21 family members of patients with PSP including 3 previous considered as sporadic, 4 (19%) had history of at least one episode of PSP and 9 (43%) were FLCN mutant carriers without PSP. Seven of the nine (78%) mutant carriers had pulmonary cysts detected by high-resolution computed tomography (HRCT). Although c.924_926del and c.1611_1631del were found in eight patients from the same geographic district, haplotype analysis demonstrated that they did not share the same affected haplotype, thus excluding common ancestry. This study first demonstrates that FLCN mutation contributes to not only familial but also 'apparently sporadic' patients with isolated PSP. It suggests that mutation analysis and HRCT scan may be recommended for first-degree family members of PSP patients with FLCN mutations, irrespective of their family history status of PSP.
原发性自发性气胸（PSP）是由卵泡抑素基因（FLCN）突变引起的Birt-Hogg-Dubé综合征的常见表现，在散发性家族性PSP病例中也有发现。对102例无亲缘关系的散发性PSP中国患者及其21名家庭成员进行了FLCN的全基因分析。在5例家族性和5例散发性PSP患者中鉴定出3种新突变（c.924_926del、c.1611_1631del和c.1740C>T）和1种先前报道的突变（c.1733insC）。在PSP患者的21名家庭成员中，包括3名先前被认为是散发性的患者，4名（19%）有至少一次PSP发作史，9名（43%）是无PSP的FLCN突变携带者。9名突变携带者中有7名（78%）通过高分辨率计算机断层扫描（HRCT）检测到肺囊肿。尽管在来自同一地理区域的8名患者中发现了c.924_926del和c.1611_1631del，但单倍型分析表明他们不共享相同的受影响单倍型，因此排除了共同祖先。本研究首次证明，FLCN突变不仅导致散发性PSP家族患者，也导致“明显散发性”患者。这表明，对于有FLCN突变的PSP患者的一级家庭成员，无论其PSP家族史状况如何，都可能建议进行突变分析和HRCT扫描。
