Respirology Department, Children's Hospital of Fudan University, Shanghai, P.R. China.
Cardiothoracic Surgery Department, Children's Hospital of Fudan University, Shanghai, China.
J Pediatr. 2020 Oct;225:157-165.e5. doi: 10.1016/j.jpeds.2020.05.052. Epub 2020 Jun 2.
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.
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.
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.
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.
报告中国儿童原发性纤毛运动障碍（PCD）的临床表现、纤毛表型、遗传谱以及表型/基因型相关性的详细知识。
我们招募了 50 名中国儿童 PCD 患者。对这些患者进行了广泛的临床评估、鼻一氧化氮、高速视频分析、透射电镜和基因检测，以描述其表型和基因型。
常见的临床特征包括慢性湿咳（85.4%）、侧位缺陷（70.0%）和新生儿呼吸窘迫（55.8%）。在接受全面合并症检查的患者中，先天性异常的患病率较高（30.2%，13/43），包括胸廓畸形（11.6%，5/43）、先天性心脏病（9.3%，4/43）和感觉神经性耳聋（2.3%，1/43）。对于 24 名年龄>6 岁的儿童，1 秒用力呼气量的平均预测值为 87.2%。42 例患者中有 38.1%（16/42）报告存在高分辨率计算机断层扫描支气管扩张。在 13 个基因中发现了双等位基因突变（总计 81 个，其中 57 个为新突变）：DNAAF3、DNAAF1、DNAH5、DNAH11、CCDC39、CCDC40、CCDC114、CCDC103、HYDIN、CCNO、DNAI1、OFD1 和 SPAG1。总的来说，纤毛超微结构和跳动模式与基因型很好地相关。然而，在 CCDC39 和 DNAH5 突变纤毛中也观察到了可变的表型。
中国这一大 PCD 队列扩大了儿童 PCD 的临床、纤毛表型和遗传特征。除了一些特殊性，如相关异常的高患病率外，我们的发现与之前的研究大致一致。
