中国原发性纤毛运动障碍患儿纤毛超微结构及基因分析  

Ciliary ultrastructure and genetic spectrum of children with primary ciliary dyskinesia in China

作　　者：刘璇 舒畅[1] Liu Xuan;Shu Chang(Department of Respiratory,Children's Hospital of Chongqing Medical University,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属儿童医院呼吸科、儿童发育疾病研究教育部重点实验室、国家儿童健康与疾病临床医学研究中心、儿童发育重大疾病国家国际科技合作基地、儿科学重庆市重点实验室,重庆400010

出　　处：《国际呼吸杂志》2022年第21期1601-1610,共10页International Journal of Respiration

基　　金：重庆市科卫联合医学科研项目(2019MSXM009)

摘　　要：目的探讨中国原发性纤毛运动障碍(PCD)患儿纤毛超微结构及基因变异特点。方法搜集重庆医科大学附属儿童医院呼吸中心2018年11月至2021年5月经支气管黏膜活检纤毛透射电子显微镜检查及第二代全外显子trio家系测序的8例PCD患儿资料,在国内外数据库PubMed、中国知网、维普、万方进行文献检索,检索时间为自数据库建库起至2021年9月,结合相关报道完善纤毛活检及基因检测的中国PCD患儿资料,总结其基因突变和纤毛结构的关系。结果8例患儿确诊中位年龄为6.25岁,其中男6例,女2例,大多有慢性咳嗽、慢性鼻-鼻窦炎、支气管扩张,伴全内脏转位2例。支气管纤毛透射电子显微镜结果示支气管黏膜纤毛内、外动力臂(IDA+ODA)缺陷5例,IDA缺陷1例,纤毛数量减少1例,正常1例。完善基因分析,共检测出致病基因突变10个,其中DNAH5检测到新发致病突变1个:c.11029-2A>T(剪切突变)。通过文献复习并结合本文病例,共纳入80例同时完善了纤毛活检及基因检测的中国PCD患儿,其中DNAH5、DNAH11、HYDIN基因为中国患儿常见突变基因,ODA缺陷(26.25%,21/80)、IDA缺陷+微管紊乱(25.00%,20/80)是中国患儿常见的纤毛超微结构缺陷,有16.25%(13/80)PCD患儿纤毛超微结构正常。结论对致病基因与纤毛超微结构统计分析,大多PCD相关基因突变可通过其编码蛋白的位置及功能,从而预测纤毛超微结构的变化。PCD"标志性"纤毛超微结构缺陷检出率70.00%(56/80),16.25%(13/80)PCD患儿纤毛超微结构正常,提示纤毛活检并非PCD的"金标准",在患儿临床表现符合PCD典型症状时,即使纤毛透射电子显微镜下结构正常,仍不能排除PCD,基因分析也是PCD诊断的重要手段。Objective To explore the ciliary ultrastructure and gene mutation of children with primary ciliary dyskinesia(PCD)in China.Methods The clinical data of 8 PCD children who had undergone ciliary biopsy of the bronchial mucosa by transmission electron microscopy(TEM)and Trio-based whole-exome sequencing(trio-WES)in the Respiratory Center,Children′s Hospital of Chongqing Medical University from November 2018 to May 2021 was analyzed.The literature retrieval was carried out from the Chinese and foreign databases including"PubMed","CNKI","VIP"and"Wanfang"during the inception to September 2021.The ciliary biopsy and genetic testing-related reports of PCD children in China was perfected to summarize the relationship between genetic mutations and ciliary ultrastructure.Results In 8 confirmed case,the median age was 6.25 years old,6 males and 2 females,chronic cough,chronic rhinosinusitis and bronchiectasis was the main clinical symptoms,complete transposition of the viscera in 2 cases.The result of TEM identified that 5 cases of ciliary inner and outer dynein arms(IDA+ODA)defects,1 case of IDA defects,1 case of reduced ciliary and 1 case of normal ciliary.Ten disease-causing gene mutation were detected,including a novel pathogenic mutation c.11029-2a>t(splicing mutation)in DNAH5 gene.Based the case of this article,the article reviewed eligible 80 PCD children in China who had undergone ciliary biopsy and genetic testing.DNAH5,DNAH11 and HYDIN genes were common mutant genes in PCD children in China.ODA defects(26.25%,21/80)and IDA defects+microtubule disorganization(25.00%,20/80)were common ciliary ultrastructural defects in PCD children in China,and 16.25%(13/80)of normal ciliary ultrastructure.Conclusions According to the statistical analysis of pathogenic genes and ciliary ultrastructure,most PCD related gene mutations can predict the changes of ciliary ultrastructure through the location and function of their coding proteins.The detection rate of"landmark"ciliary ultrastructure defects of PCD was 70.00%(56/80).The ci

关 键 词：纤毛运动障碍 基因 显微镜检查 电子 透射 纤毛结构 

分 类 号：R272[医药卫生—中医儿科学]