摘要
目的研究表面活性物质功能障碍的基因突变与儿童间质性肺疾病（ILD）的关系。
方法将2012年1月至2017年12月首都医科大学附属北京儿童医院收治的26例2岁前发病或病理诊断仍未明确病因的ILD患儿进行相关基因，如表面活性物质蛋白B基因（surfactant protein B，SFTPB）、表面活性物质蛋白C基因（surfactant protein C，SFTPC）、三磷酸腺苷结合盒转运子A3基因（ATP binding cassette transporter A3，ABCA3）的全部外显子和相邻的内含子的基因突变检测，对基因突变结果及临床资料进行研究分析。基因分析方法：对检测基因进行PCR扩增，并进行Sanger测序。
结果1.共发现4例确定的表面活性物质功能障碍的基因突变病例，其中发现3例有致病意义的SFTPC3基因突变，即c.218T〉C突变、IVS4，＋1G〉C突变；c.115G〉T各1例。发现1例ABCA3基因复合杂合突变，即c.3913 T〉C和外显子13－18存在杂合缺失。2.不能确定或可疑的7例病例，包括4例不确定意义SFTPC基因突变，分别为c.406G〉C，IVS4，＋12 T〉G，c.364T〉C，c.68G〉A突变。3例检测到2个ABCA3的杂合突变，但未行父母验证。1例患儿同时有SFTPC的IVS4，＋12 T〉G和ABCA3 c．737C〉T杂合突变，该患儿的肺病理为淀粉样变，有类似疾病家族史。3.有15例未找到致病意义表面活性物质功能障碍的基因突变。未测到SFTPB基因的有意义突变。确定致病基因突变2例（1例SFTPC c．115G〉T和1例ABCA3复合杂合突变）进行了肺组织活检，肺组织均为非特异性间质性肺炎（nonspecific interstitial pneumonia，NSIP），其中SFTPC c．115G〉T、IVS4，＋1G〉C各1例突变已死亡，死亡年龄分别为14岁和11个月，仅1例SFTPC c．218T〉C突变有家族史，激素治疗后治愈。另1例ABCA3复合杂合突变出生后即出现新生儿呼吸窘迫综合征，之后呼吸困难、乏力，经激素治疗稍有改善。4例胸部CT/高分辨计�
ObjectiveTo study the genetic mutation of surfactant dysfunction in children with interstitial lung disease.MethodsThe 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 hete-rozygous deletion in Exon 13-18.（2）There were also 7 uncertain or suspected cases.Four cases were undefined pa-thogenic 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 mu
作者
王俊芳
刘秀云
殷菊
刘军
申昆玲
Wang Junfang, Liu Xiuyun, Yin Ju, Liu Jun, Shen Kunling(National Children＇s Medical Center, Department of Respiratory, Beijing Children＇s Hospital, Capital Medical University, National Clinical Research Center for Respiratory Diseases ,Beijing 100045, China Wang JF（ Present Work Unit ：Depart- ment of Pediatrics, Shijingshan Teaching Hospital of Capital Medical University, Shijingshan Hospital）, Liu XY, Yin J, Liu J , Shen KL)
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2018年第4期300-305,共6页
Chinese Journal of Applied Clinical Pediatrics
