Clinical and Genetic Spectrum of Children with Primary Ciliary Dyskinesia in China
Clinical and Genetic Spectrum of Children with Primary Ciliary Dyskinesia in China
复制标题
中国原发性纤毛运动障碍儿童的临床和遗传谱
DOI：
10.1016/j.jpeds.2020.05.052
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发表时间：
2020-10-01
影响因子：
5.1
通讯作者：
Qian, Liling
中科院分区：
文献类型：
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作者：
Guo, Zhuoyao;Chen, Weicheng;Qian, Liling
目的了解中国儿童原发性睫状体运动障碍(PCD)的临床表现、纤毛表型、遗传谱及表型/基因相关性。临床表现包括慢性湿咳(85.4%)、偏侧畸形(70.0%)和新生儿呼吸窘迫(55.8%)。在接受综合检查的患者中，先天性畸形的发生率较高(30.2%，13/43)，包括胸部畸形(11.6%，5/43)、先天性心脏病(9.3%，4/43)和感音神经性聋(2.3%，1/43)。24名6岁儿童的1秒用力呼气量预测值平均值为87.2%。在高分辨率计算机断层扫描中，38.1%(16/42)的患者出现明显的支气管扩张。在DNAAF3、DNAAF1、DNAH5、DNAH11、CCDC39、CCDC40、CCDC114、CCDC103、HYDIN、CCNO、DNAI1、OFD1和SPAG1等13个基因上发现了双等位基因突变(共81个，新发现57个)。总体而言，纤毛超微结构和节拍模式与基因型有很好的相关性。结论中国的这一庞大的PCD队列扩大了儿童PCD的临床、纤毛表型和遗传特征。我们的发现与以前的研究大致一致，除了一些特殊的特征，如相关异常的高患病率。
Objective To report detailed knowledge about the clinical manifestations, ciliary phenotypes, genetic spectrum as well as phenotype/genotype correlation in primary ciliary dyskinesia (PCD) in Chinese children.Study design We recruited 50 Chinese children with PCD. Extensive clinical assessments, nasal nitric oxide, high-speed video analysis, transmission electron microscopy, and genetic testing were performed to characterize the phenotypes and genotypes of these patients.Results Common clinical features included chronic wet cough (85.4%), laterality defects (70.0%), and neonatal respiratory distress (55.8%). A high prevalence of congenital abnormalities (30.2%, 13/43), observed in patients who underwent comprehensive examination for comorbidities, included thoracic deformity (11.6%, 5/43), congenital heart disease (9.3%, 4/43), and sensorineural deafness (2.3%, 1/43). For 24 children age >6 years, the mean predicted values of forced expiratory volume in 1 second were 87.2%. Bronchiectasis evident on high-resolution computed tomography was reported in 38.1 % of patients (16/42). Biallelic mutations (81 total; 57 novel) were identified in 13 genes: DNAAF3, DNAAF1, DNAH5, DNAH11, CCDC39, CCDC40, CCDC114, CCDC103, HYDIN, CCNO, DNAI1, OFD1, and SPAG1. Overall, ciliary ultrastructural and beat pattern correlated well with the genotype. However, variable phenotypes were also observed in CCDC39 and DNAH5 mutant cilia.Conclusions This large PCD cohort in China broadens the clinical, ciliary phenotypes, and genetic characteristics of children with PCD. Our findings are roughly consistent with previous studies besides some peculiarities such as high prevalence of associated abnormalities.