[Cilia ultrastructural and gene variation of primary ciliary dyskinesia: report of three cases and literatures review].

Objective: To analyze the clinical manifestations, cilia ultrastructure and gene variations of primary ciliary dyskinesia (PCD). Methods: Analysis of three cases diagnosed as PCD by transmission electron microscopy of the endobronchial biopsy material in Division of Pediatric Pulmonology of Shandong Provincial Hospital between 2013 and 2016. Target gene sequence capture and next generation sequencing were used to analyze the gene. Related literatures on gene variation of PCD in Chinese were reviewed from Online Mendelian Inheritance in Man, Human Gene Mutation Database, PubMed and CNKI up to July 2017 by using search terms of "PCD" , "gene" , "Chinese". Results: There were one male and two females aged from 10 to 11 years. The common symptoms included recurrent respiratory infection, sinusitis and bronchiectasis. Two of them had situs inversus. Case 1 had lack of outer and inner dynein arms with compound heterozygous mutation of LRRC6. Case 2 had outer and inner dynein arms defects with heterozygous mutations of DNAH5 and DNAH11. Case 3 had abnormality in microtubule and inner dynein arms with homozygous mutation of CCDC39. All the variations mentioned above have not been reported before. Twelve cases have been reported about gene variations in PCD in Chinese from eight reports. All these patients had recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis. Nine of them had dextrocardia. Four cases have taken an effective nasal (or bronchial) mucosal biopsy. 1 case had inner and outer dynein arms defects. One case had inner dynein arms and radial spokes defects. One case had microtubule and central pair defects. And 1 case had normal cilia ultrastructure. Eight kinds of gene variations were found. Three cases had gene variations of DNAH5. 2 cases had gene variations of DYX1C1. 2 cases had gene variations of CCNO. There was 1 case with gene variations of CCDC39, CCDC40, HYDIN, ARMC4 and DNAI1 separately. Conclusions: Recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis are the common symptoms of PCD. Eleven of fifteen Chinese PCD patients with positive gene mutations were Kartagener syndrome. Cilia ultrastructure showed defects of inner and outer dynein arms, radial spokes, microtubule and central pair. Ten kinds of gene variations were found: DNAH5, DYX1C1, CCNO, CCDC39, CCDC40, HYDIN, ARMC4, DNAI1, LRRC6、DNAH11.目的： 探讨原发性纤毛运动障碍（PCD）临床、纤毛结构缺陷及基因变异特点。 方法： 对山东大学附属省立医院小儿呼吸科2013—2016年通过支气管黏膜活检纤毛电镜诊断的3例PCD患儿采用靶向目标捕获二代测序行基因检测，分析其临床表现、纤毛结构和基因变异特点，通过关键词"PCD""gene""Chinese"对在线人类孟德尔遗传数据库、人类基因组变异数据库、PubMed和中国知网建库至2017年7月的文献进行检索，分析总结已报道的中国PCD患者基因变异的病例资料。 结果： 3例患儿年龄10~11岁，1男2女，均有反复呼吸道感染、慢性鼻-鼻窦炎、支气管扩张，2例伴全内脏转位。例1支气管黏膜纤毛内外动力蛋白臂缺失，LRRC6基因复合杂合变异；例2支气管黏膜纤毛内外动力蛋白臂缺失，DNAH5和DNAH11基因杂合变异；例3支气管黏膜纤毛微管数目异常和内动力蛋白臂缺陷，CCDC39基因纯合变异。3例基因变异位点均为未报道的新变异。检索共筛选出8篇文献，共报道12例基因变异的PCD中国患者，均存在自幼反复呼吸道感染、慢性鼻-鼻窦炎、支气管扩张，其中合并右位心9例。4例进行了有效的鼻（或支气管）黏膜纤毛活检，纤毛内外动力蛋白臂缺失1例，内动力蛋白臂和放射辐缺失1例，外周微管对和中央微管对部分缺失1例，纤毛结构正常1例。共发现PCD相关致病基因变异8种，DNAH5基因变异3例，DYX1C1基因变异2例，CCNO基因变异2例，CCDC39、CCDC40、HYDIN、ARMC4、DNAI1基因变异各1例。 结论： PCD临床表现为自幼反复呼吸道感染、慢性鼻-鼻窦炎、支气管扩张。15例发现基因变异的中国PCD患者中11例为Kartagener综合征患者，纤毛结构可有内外动力蛋白臂、放射辐、外周微管对及中央微管对的缺陷，15例共发现10种PCD相关致病基因变异：DNAH5、DYX1C1、CCNO、CCDC39、CCDC40、HYDIN、ARMC4、DNAI1、LRRC6、DNAH11。.