This report entails a case of an 11-year-old Chinese boy with cystic fibrosis (CF), who bears the c.1521_1523delCTT/c.3874-4522A>G genotype, which is extremely rare in Chinese population. Notably, the deep intron mutation c.3874-4522A>G was the first time identified among Chinese patients, which was reported mainly associated with mild phenotype. It is generally considered that a mild allele sustains CFTR function in a dominant fashion, even if paired with a severe allele. However, in the present report, the c.3874-4522A>G mutation was found related to severe pulmonary diseases, including early symptom onset, progressive bronchiectasis, recurrent airway P. aeruginosa combined with MRSA, rapid decline of lung function, and poor weight gain, which suggesting severe phenotype. Despite intensive chest care and optimized therapy, the child ultimately died of cardiopulmonary failure 3 months after discharge.

Objective: To investigate the clinical manifestations, diagnosis and treatment processes of two siblings with PCD caused by the same compound heterozygous mutations in DNAAF2. Methods: With clinical diagnosis of PCD, the two siblings were recruited in the study. We collected their clinical histories, laboratory tests, bronchoscopy, otoscope images, and radiographic data. Whole blood of the siblings and their parents were separately harvested for whole-exome sequencing and Sanger sequencing. Results: The 7-year-old girl presented with recurrent respiratory tract infection, sinusitis and otitis media. Auxiliary examinations showed pneumonia, atelectasis, bronchiectasis, low nitric oxide concentration (nNO), and conducting hearing loss. The younger brother, 10-month boy, exhibited pneumonia, sinusitis, otitis media, intestine malrotation and with lower nNO, atelectasis in chest CT, obstructive ventilator dysfunction by pulmonary function and conductive hearing loss. Two compound heterozygous mutations in DNAAF2 were detected in both of the siblings, nonsense mutation c.156C＞A and frameshift mutation c.177_178insA, and the c.177_178insA (p.E60Rfs*3) mutation is a novel mutation. Conclusion: The study enriches our knowledge of clinical manifestations and genetic information of PCD caused by DNAAF2.

Objectives: To characterize the clinical and genotypic features of Cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS) in Chinese children. Methods: We recruited and characterized the clinical manifestations of 11 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and sanger sequencing validation was performed to define the genotypes. Results: CF-PBS was accompanied by recurrent and/or persistent pneumonia (100%), pancreatitis (81.8%), vomit and/or diarrhea (63.6%), failure to thrive (FTT) (63.6%) and liver disease (54.5%) among our patients. The predominant organisms found in the airways was Pseudomonas aeruginosa (90.9%) and Staphylococcus aureus (81.8%). The mean concentration of blood gas and electrolytes were: PH 7.58, bicarbonate 40.8 mmol/L, sodium 126.7 mmol/L, chloride 80.0 mmol/L, and potassium 2.7 mmol/L, respectively. A high recurrence rate (54.5%) of PBS was observed despite continued electrolyte supplementation during follow up. 17 different mutations of CFTR gene were identified, and 9 of them turned out to be novel observations (c.262_266delTTATA, c.579+2insACAT, c.1210-3C>G, c.1733T>C, c.2236_2246delGAGGCGATACTinsAAAAATC, c.3635delT, c.3859delG, c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A/p.G970D was the most common mutation, with an allele frequency of 18.2%. c.1521_1523delCTT/p.F508del was the first time found with homozygous genotype in patients of Chinese origin. Conclusions: In China, CF-PBS always occurs early and repeatedly in infancy, accompanied by the high frequency of multi-system co-morbidities. Recurring in school-age patients is rare but does exist. The c.2909G>A/p.G970D is the most frequent mutation in Chinese patients with CF-PBS, showing a significant ethnic tendency of Chinese origin.