SFTPC基因p.K114N新发突变致儿童间质性肺疾病一家系分析  

Analysis of the pedigree of a child with interstitial lung disease caused by a novel mutation of p.K114N in SFTPC gene

作　　者：段效军[1] 张喜[1] 孟燕妮[1] 张瑾 李林瑞[1] 施玹 陈璐[1] 陈艳萍[1] Duan Xiaojun;Zhang Xi;Meng Yanni;Zhang Jin;Li Linrui;Shi Xuan;Chen Lu;Chen Yanping(Department of Respiratory,Hunan Children′s Hospital,Changsha 410007,China)

机构地区：[1]湖南省儿童医院呼吸内科,长沙410007

出　　处：《中国小儿急救医学》2021年第6期487-491,共5页Chinese Pediatric Emergency Medicine

基　　金：湖南省卫健委一般资助课题(20200609)。

摘　　要：目的:报道1例儿童间质性肺疾病家系的临床及胸部CT影像学特点,并对患儿及其家系进行致病基因突变分析。方法:为明确先证者间质性肺疾病的致病原因,对患儿的家系展开调查,采集5例先证者家系成员的临床资料,并对4例有呼吸道症状的家系成员进行胸部HRCT检查;进一步对先证者血样进行人类全外显子测序进行致病性分析,且对其及其家属进行一代验证。结果:家系调查发现,该家系7人中存在5例间质性肺疾病患者,男性3例,女性2例,其中1例死亡。4例存活的患者均存在SFTPC基因突变(exon4,c.342G>T,p.K114N),考虑变异来源于先证者父亲,为致病性突变,其在各数据库中无收录,为新发突变。并且家系中不同患者的表现度存在明显差异。结论:SFTPC基因p.K114N新发突变可导致儿童间质性肺疾病,且该突变在家系成员中存在外显不全现象,胸部CT和全外显子测序对儿童间质性肺疾病的诊断具有重要意义。Objective To analyze the clinical and chest CT features in a family with interstitial lung disease(ILD),and assess the probable causative gene mutations for the family.Methods In order to identify the etiology of the proband′s ILD,the pedigree was investigated.The clinical data of five proband′s pedigree members were collected,and the chest HRCT examination was performed on four proband′s pedigree members with respiratory symptoms.The human whole exon sequencing was performed on the proband′s blood samples,then its deleterious effects were assessed.Subsequently,the strong pathogenic mutation was validated by Sanger sequencing.Results According to the family survey,there were five patients with ILD in the family,including three males and two females.One of them died.The surfactant protein C(SFTPC)gene(exon4,c.342G>T,p.K114N)was found in all four surviving patients.The mutation was considered to be originated from the father of the proband,and the pathogenic mutation was considered,which was not included in the databases and was a noval mutation.In addition,the clinical manifestations of different patients in the family were significantly different.Conclusion The novel mutation of p.k114n in SFTPC gene can lead to ILD in children,and the mutation has incomplete exons in family members.Chest CT and whole exon sequencing play an important role in the diagnosis of ILD in children.

关 键 词：间质性肺疾病 儿童 表面活性蛋白C 基因 新发突变 

分 类 号：R725.6[医药卫生—儿科]