Clinical and genetic spectrum of interstitial lung disease in Chinese children associated with surfactant protein C mutations
Clinical and genetic spectrum of interstitial lung disease in Chinese children associated with surfactant protein C mutations
复制标题
表面活性蛋白C突变相关的中国儿童间质性肺病的临床和遗传谱
DOI：
10.1186/s13052-019-0710-2
复制
发表时间：
2019-08-28
影响因子：
3.6
通讯作者：
Qian, Liling
中科院分区：
文献类型：
--
作者：
Hong, Da;Dai, Dan;Qian, Liling
表面活性蛋白C基因（SFTPC）突变导致间质性肺疾病（ILD）。我们的目的是描述与SFTPC突变相关的中国儿童ILD的临床和遗传谱。方法选取6例SFTPC突变杂合子ILD患儿。通过下一代测序对负责表面活性剂功能障碍的候选基因进行测序。产生具有新突变的SFTPC亚克隆并瞬时转染入A549细胞。采用免疫印迹和免疫荧光法对突变型表面活性蛋白C（SP-C）的功能进行了鉴定。结果发病年龄7天~ 15个月。所有病例均需要补充氧气。发育不良（5/6）是最显著的肺外表现。在4例患者中给予羟氯喹作为肺部疾病的长期治疗，其中2例反应良好。在6例患者中鉴定出3种突变：4例为I73 T，1例为D105 G，1例为Y113 H。三名患者的突变是遗传性的，三名是新生的。Western blotting显示突变体SP-C（D105 G和Y113 H）与野生型SP-C的带型完全不同。免疫荧光显示突变体SP-C（D105 G）几乎不被运输到板层体，但很好地定位于早期内体，这与野生型蛋白形成鲜明对比。结论SFTPC基因突变是中国儿童ILD的重要病因。I73 T是中国ILD儿童中常见的SFTPC突变，与表面活性蛋白C突变相关。
Background Mutations in the surfactant protein C gene (SFTPC) result in interstitial lung disease (ILD). Our objective was to characterize clinical and genetic spectrum of ILD in Chinese children associated with SFTPC mutations. Methods Six Chinese children with ILD heterozygous for SFTPC mutations were included. Candidate genes responsible for surfactant dysfunction were sequenced by next-generation sequencing. Subclones of SFTPC with novel mutations were generated and transiently transfected into A549 cells. The functional characterization of mutant surfactant protein C (SP-C) was evaluated by Western blotting and immunofluorescence. Results The age of onset ranged from 7 days to 15 months. All cases required supplemental oxygen. Failure to thrive (5/6) was the most significant extra-pulmonary manifestation. Hydroxychloroquine was given as the long-term treatment of lung disease in four patients and two of them responded well. Three mutations were identified in six patients: four with I73T, one with D105G, one with Y113H. Mutations in three patients were inherited and three arised de novo. Western blotting revealed totally different band patterns between mutant SP-C (D105G and Y113H) and the wildtype. Immunofluorescence showed mutant SP-C (D105G) was scarcely trafficked to lamellar bodies but localized well to early endosomes, which was in marked contrast to the wildtype protein. Conclusion SFTPC mutations were an important cause of childhood ILD in Chinese population. I73T was a common SFTPC mutation in Chinese ILD children associated with surfactant protein C mutations.