Study on genetic mutation of surfactant dysfunction in children with interstitial lung disease / 中华实用儿科临床杂志

ABSTRACT

Objective To study the genetic mutation of surfactant dysfunction in children with interstitial lung disease.Methods The surfactant protein B (SFTPB),surfactant protein (SFTPC),ATP binding cassette transporter A3 (ABCA3) gene sequence detection were conducted for 26 patients with interstitial lung disease who were onset before 2 years old or without specific etiology after the biopsy during January 2012 to December 2017 in Beijing Children's Hospital Affiliated to Capital Medical University,then the result of gene sequence detection and the clinical data were analyzed.The method of gene analysis is PCR amplify and Sanger sequencing.Results (1) In total,4 cases of abnormal gene mutations had been found,of which 3 cases were pathogenic SFTPC gene mutations,such as c.218T ＞ C,IVS4,+ 1G ＞ C,c.115G ＞ T,1 case was ABCA3 compound heterozygous mutations,such as C.3913 T ＞ C and heterozygous deletion in Exon 13-18.(2)There were also 7 uncertain or suspected cases.Four cases were undefined pathogenic SFTPC mutations,such as c.406G ＞ C,IVS4,+ 12 G ＞ G,c.364T ＞ C,c.68G ＞ A.Three cases had been found with two ABCA3 heterozygous gene mutations,which were not confirmed by parents.The lung pathology of the patient with SFTPC (IVS4,+ 12 T ＞ G) and heterozygous ABCA3 (c.737C ＞ T)gene mutations was amyloidosis,and there was similar history in his family.(3) No pathogenic gene mutation was found in the 15 cases.No pathogenic SFTPB gene mutation was found in all the patient.Lung biopsy was performed in 2 cases of SFTPC c.115G ＞ T and ABCA3 compound heterozygous mutation,the lung tissue of this 2 cases were nonspecific interstitial pneumonia (NSIP).One case of SFTPC c.115G ＞ T had died at the age of 14 years old and 1 case of IVS4,+ 1G ＞ C had died at the age of 11 months old.Only 1 case of SFTPC c.218T ＞ C gene mutation with the similar family history,had improved significantly after glucocorticoid treatment,another case of ABCA3 compound heterozygous mutation was mildly improved after the glucocorticoid treatment.The chest CT/high resolution computed tomography displayed diffuse ground glass opacity in 4 cases,and cystic in 2 cases,all 2 cases with cystic were cases of SFTPC mutation and were dead.Conclusions The gene mutation of surfactant dysfunction is associated with interstitial lung disease in children.The pathology feature can be NSIP,and the prognosis may be poor in some cases,and the treatment of the corticosteroids may be effective in few case.