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Genetic risk factors for spontaneous pneumothorax in Birt-Hogg-Dubé syndrome.

Birt-Hogg-dub é 综合征自发性气胸的遗传危险因素。

  • 影响因子:3.84
  • DOI:10.1016/j.chest.2019.12.019
  • 作者列表:"Sattler EC","Syunyaeva Z","Mansmann U","Steinlein OK
  • 发表时间:2020-01-17
Abstract

BACKGROUND:Birt-Hogg-Dubé syndrome (BHDS) is a genetic tumor syndrome characterized by lung cysts, spontaneous pneumothorax, fibrofolliculoma and renal cell cancer. Due to its rarity and clinical heterogeneity, much is still unknown regarding the course of the disease and individual risk assessment. Therefore, we studied non-environmental risk factors for pneumothorax in a large sample of BHDS patients. METHODS:Clinical data were available from 197 BHDS patients (male 103, female 94) belonging to 63 unrelated families. The FLCN coding region including adjacent intronic sequences was analysed by PCR and subsequent Sanger sequencing as well as MLPA. Statistical analyses were performed using adequate methods to account for familial clustering. RESULTS:Patients who had only a single spontaneous pneumothorax were significantly older at the time of occurrence than those with multiple ones (mean 38.93 versus 29.74 years, p-value 0.010). The risk for three or more pneumothoraces drastically increased after the second event. Significantly increased pneumothorax risks were found for mutations c.1300G>C (59%) and c.250-2A>G (77%), compared to FLCN hotspot mutation c.1285dup (37% risk) (p-value 0.02). CONCLUSIONS:We observed significant differences for the spontaneous pneumothorax risk regarding both age and gender in BHDS patients. Furthermore, two FLCN mutations were identified that are associated with significantly increased pneumothorax risk. Thus, formerly unknown individual predictors have been identified that provide improved risk stratification for BHDS patients.

摘要

背景: Birt-Hogg-dub é 综合征 (BHDS) 是一种以肺囊肿、自发性气胸、纤维滤泡瘤和肾细胞癌为特征的遗传性肿瘤综合征。由于其罕见性和临床异质性,关于病程和个体风险评估仍有许多未知。因此,我们在一个大样本的 BHDS 患者中研究了气胸的非环境危险因素。 方法: 临床资料来自 63 个无关家族的 197 例 BHDS 患者 (男性 103 例,女性 94 例)。通过 PCR 和随后的 Sanger 测序以及 MLPA 分析包括相邻内含子序列的 FLCN 编码区。使用适当的方法进行统计分析,以解释家族聚集性。 结果: 只有单个自发性气胸的患者在发生时明显比多个自发性气胸的患者年龄大 (平均 38.93 对 29.74 年,p 值 0.010)。第二次事件后,发生三次或更多次肺炎的风险急剧增加。与 FLCN 热点突变 c.1285dup (59% 风险) 相比,发现突变 c.1300G> C (77%) 和 c.250-2A> G (37%) 的气胸风险显著增加 (p 值 0.02)。 结论: 我们观察到 BHDS 患者的自发性气胸风险在年龄和性别方面存在显著差异。此外,确定了两个与气胸风险显著增加相关的 FLCN 突变。因此,以前未知的个体预测因子已经被确定,为 BHDS 患者提供了改善的风险分层。

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