Identification of a Missense Mutation in the Surfactant Protein A2 Gene in a Chinese Family with Interstitial Lung Disease
Identification of a Missense Mutation in the Surfactant Protein A2 Gene in a Chinese Family with Interstitial Lung Disease
复制标题
一个中国间质性肺病家系表面活性蛋白A2基因错义突变的鉴定
DOI：
10.1089/dna.2020.6045
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发表时间：
2020-11-12
影响因子：
3.1
通讯作者：
Luo, Hong
中科院分区：
文献类型：
--
作者：
Liu, Lv;Liu, Yi-Jie;Luo, Hong
间质性肺病 (ILD) 是一大类疾病，其中大多数会导致肺组织进行性疤痕形成。与 ILD 相关的疤痕最终会影响您的呼吸能力以及将足够氧气输送到血液中的能力。 ILD 的典型症状是休息时呼吸短促或劳累时呼吸急促以及干咳。在这项研究中，我们招募了一个来自中国中南地区的 ILD 家庭。 3名患者出现反复咳嗽和呼吸急促的症状。高分辨率计算机断层扫描（HRCT）测试进一步证实了肺间质病变的诊断。应用全外显子组测序（WES）和桑格测序来检测该家系的遗传病变。通过采用 WES，在受影响的个体中发现了表面活性剂蛋白 A2 (SFTPA2) 的新杂合突变 (NM_001098668: c.554C>T/p.A185V)，而在健康成员中则不存在。生物信息学分析预测该突变为致病突变，位于SFTPA2蛋白的进化保守位点。这种新的突变可能会破坏SFTPA2蛋白的稳定性并诱导内质网应激，最终在微生物的影响下导致ILD。我们的研究不仅扩大了 SFTPA2 突变谱，还帮助家庭成员减轻 ILD 危险因素。该研究还补充和完善了中国的基因检测策略和ILD风险评估方法。
Interstitial lung disease (ILD) is a large group of disorders, most of which lead to progressive scarring of lung tissue. The scarring associated with ILD eventually affects your ability to breathe and get enough oxygen into your bloodstream. The typical symptoms of ILD are shortness of breath at rest or aggravated by exertion and dry cough. In this study, we enrolled a family with ILDs from central south region of China. Three patients suffered from repeated cough and shortness of breath. The high resolution computed tomography (HRCT) testing further confirmed the diagnosis of interstitial lung lesions. Whole exome sequencing (WES) and Sanger sequencing were applied to detect the genetic lesion of the family. By employing WES, a novel heterozygous mutation (NM_001098668: c.554C>T/p.A185V) of surfactant protein A2 (SFTPA2) was identified in the affected individuals and absent in the healthy members. Bioinformatics analysis predicted that this mutation is disease-causing mutation and located in an evolutionarily conserved site of SFTPA2 protein. The novel mutation may disrupt the stability of SFTPA2 protein and induce endoplasmic reticulum stress, finally leading to ILD under the influence of microorganisms. Our study not only expands the spectrum of SFTPA2 mutations but also helps the family members to mitigate ILD risk factors. The study also supplements and improves genetic testing strategies and ILD risk estimation methodologies for China.