Application Of Genetic Testing In The Diagnosis Of Diffuse Cystic Lung Disease

Objectives:Diffuse cystic lung disease(DCLD)is a group of disorders 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 and gene testing may 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 advices 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 whole exon sequencing.24 patients(23.3%)were diagnosed with Birt-Hogg-Dube(BHD)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.Conclusions:(1)Genetic testing used in the screening of BHD syndrome,plays an important role in reducing missed diagnosis.(2)The potential pathogenic mutations found in genetic testing provide directions for further clinical evaluation;(3)The establishment of a diagnostic process combining clinical diagnosis and genetic diagnosis of DCLD is helpful for the etiology screening of patients with DCLD,so as to provide a basis for applying genetic testing as a screening method for DCLD patients.