Clinical and Genetic Spectrum of Children with Primary Ciliary Dyskinesia in China

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.