Characterization of clinical and genetic spectrum of Chinese patients with cystic fibrosis

Cystic fibrosis (CF) is a rare autosomal recessive disorder caused by biallelic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The clinical features and mutation spectrum of CF have been well characterized in Caucasians, while limited studies were conducted in Chinese patients. A total of 20 individuals from 19 families were diagnosed with CF in this study. We analyzed the clinical features and screened all coding exons of CFTR using a combination of Sanger sequencing and multiplex ligation-dependent probe amplification analysis. The median age at onset was 9.3 years in our cohort, while the median age at diagnosis was 19 years. The respiratory system was most frequently affected in this study: all patients (100%, 19/19) presented diffuse bronchiectasis and 61.1% (11/18) of patients showed a forced expiratory volume in 1 s below 80% predicted. Six patients (6/20, 30%) exhibited allergic bronchopulmonary aspergillosis (ABPA). Only 4 (4/20, 20%) patients presented pancreatic exocrine insufficiency (PI). Three adult male patients receiving examinations for congenital bilateral absence of the vas deferens were all found positive for the condition. A total of 22 distinct mutations were detected in this cohort, with the variant p.G970D as the most common variant (12/38 alleles, 31.6%). Four variants (p.Y109D, p.I203F, p.D572E, and exon 2–3 deletion) were novel, which expanded the mutation spectrum of Chinese CF patients. Chinese CF patients showed different clinical features and a distinct CFTR mutation spectrum compared with Caucasians. There is a significant diagnosis delay, suggesting the current underdiagnosis of CF in China.