Interstitial lung disease (ILD) presents as progressive scarring of lung tissue, which may affect respiratory function and restrict oxygen-exchange into the bloodstream, finally leading to dyspnea, dry cough and decreased quality of life. Increasing evidence indicates that genetic factors may be crucial in the development of ILD. At present, the main pathogenic genes of ILD include genes vital for surfactant metabolism and function and telomere biology associated genes. Mutations in both sets of genes may induce the apoptosis of alveolar epithelial cells and finally result in remodeling of the lung interstitium. In this study, one Han Chinese family with interstitial pneumonia and lung cancer was recruited. The proband was selected for whole exome sequencing analysis. After data filtering, only a novel mutation (c.404G > A /p.G135E) of SFTPA2 (NM_001098668) was identified. No other meaningful mutations were detected. The mutation co-segregated with the affected patients in the pedigree and was absent in the healthy controls. Bioinformatics analysis predicted that this variant is pathogenic and located in an evolutionarily conserved site of the SP-A2 protein. This study further expands the variant spectrum of the SFTPA2 gene and may be helpful in the genetic counseling of interstitial pneumonia and lung cancer patients.

间质性肺病 (ILD) 表现为肺组织逐渐形成瘢痕，这可能会影响呼吸功能并限制氧气进入血液，最终导致呼吸困难、干咳和生活质量下降。越来越多的证据表明遗传因素可能在 ILD 的发展中起关键作用。目前，ILD的主要致病基因包括对表面活性物质代谢和功能至关重要的基因和端粒生物学相关基因。两组基因的突变均可诱导肺泡上皮细胞凋亡，最终导致肺间质重塑。在这项研究中，招募了一个患有间质性肺炎和肺癌的汉族家庭。选择先证者进行全外显子组测序分析。数据过滤后，只有一个新的突变 (c.404G > A /p.G135E)SFTPA2 (NM_001098668) 被识别。没有检测到其他有意义的突变。该突变与谱系中的受影响患者共同分离，而在健康对照中不存在。生物信息学分析预测该变异是致病性的，位于 SP-A2 蛋白的进化保守位点。本研究进一步扩展了SFTPA2基因的变异谱，可能有助于间质性肺炎和肺癌患者的遗传咨询。