目的:弥漫性囊性肺疾病（diffuse cystic lung diseases, DCLD）为ー组肺部影像 学见多发薄壁囊泡的疾病。这类疾病病因多样,包括肿瘤性疾病、遗传性疾病、 淋巴增殖性疾病、感染性疾病等。其中DCLD相关遗传性疾病种类多,且常累及 多个肺外系统,DCLD患者的临床表型常常各异,异质性高;另一方面,患者家 “成员可能未行DCLD相关筛查,或患者对家族史报告可能不完全。这些因素 使得临床工作中对导致DCLD的遗传性疾病识别困难。因此,合理的临床评估 流程对于DCLD遗传相关病因的诊断有重要意义,在临床工作中简单易行、创 伤小的检查方式更易用于病因的初步筛查。基因检测技术的成熟与广泛应用,为 导致DCLD的遗传性疾病的筛查提供了新的思路与手段。随着遗传学领域的研 究渐深,单基因检测、目标区域捕获测序（基因panel）、全外显子测序等不同方 法的基因诊断成为辅助临床诊断的重要一环。本研究旨在评估基因检测对于 DCLD遗传相关病因诊断的价值、基因检测在临床工作中的应用对象与时机,以 期为DCLD病因诊断提供建议。方法:回顾性收集2017年9月至2020年10月北京协和医院LAM门诊的DCLD 患者临床资料与基因检测数据,对患者进行临床诊断,对基因检测数据进行解读, 并与临床表型匹配,关注基因检测对于DCLD病因诊断的帮助。结果:本次纳入的103名患者中,17人（16.5%）行TSC1及TSC2基因检测, 27人A26.2%）行FLCN基因检测,48人A46.6%）行基因panel检测,11人（10.7%）行全外显子测序;共33人（32.0%）通过基因检测诊断Birt-Hogg-Dube 综合征。此外检测出除FLCN外多个基因的可疑致病突变,相应患者的最终诊断 有待进ー步临床评估。结论:（1）建立DCLD临床诊断与基因诊断相结合的诊断流程；（2）通过单基因 检测、基因panel检测、全外显子测序三种方法辅助DCLD患者遗传相关病因确 诊,评估基因诊断的价值,为将基因检测作为DCLD病因不明患者的病因筛查 手段提供依据。

Objective: Diffuse cystic lung diseases (DCLD) are a group of diseases in which multiple pulmonary cysts can be presented on computed tomography. The etiology of DCLD includes neoplastic diseases, hereditary diseases, lymphatic proliferative diseases, infectious diseases, etc. The clinical phenotypes of patients with DCLD related hereditary diseases are highly heterogeneous. And it is common that family members of patients have never been evaluated for DCLD, while some other patients may report the family history incompletely. What mentioned above poses challenges of clinical diagnosis. Therefore, a reasonable clinical evaluation process is of great significance for the diagnosis of DCLD related hereditary diseases, and less invasive examinations are easier to be accepted for patients in the preliminary screening stage. The advancement of genetic testing technology provides a new possibility. Single gene testing, gene panel examination, and whole exon sequencing (WES) have a wide range of applications and become an important step of diagnosis of hereditary diseases in DCLD patients. This study aims to evaluate the value of genetic testing in the diagnosis of DCLD related hereditary diseases, to assess who and when should accept genetic testing in clinical work, and to provide advice for the diagnosis of DCLD. Methods: Clinical and genetic testing data of patients with DCLD from LAM outpatient department of Peking Union Medical College Hospital between September 2017 to October 2020 were retrospectively collected. The patients were clinically diagnosed according to diagnostic criteria, and the genetic testing data were interpreted and matched with clinical phenotypes of the patients. Results: Among 103 patients, 17 patients (16.5%) tested gene TSC1 and TSC2. 27 patients tested gene FLCN (26.2%). 48 patients (46.6%) accepted gene panel testing. 11patients (10.7%) accepted WES. 33 patients (32.0%) were diagnosed with Birt- Hogg-Dube syndrome after genetic testing. In addition, several likely pathogenic mutations were found in other genes besides FLCN in patients though the final diagnosis of these patients needs further evaluation.Conclusion: (1) To establish the diagnostic process of DCLD by combining genetic testing with clinical evaluation; (2) Different methods of gene testing including single gene testing, gene panel examination, and whole exon sequencing were used to assist the diagnosis of the etiology of patients with DCLD related hereditary diseases, and the value of genetic diagnosis was evaluated, so as to provide a basis for applying genetic testing as a screening method for patients with unknown etiology of DCLD.