• Cystic fibrosis
• Genotype

• National Natural Science Foundation of China

• CFTR
• Chinese
• animal model
• clinical feature
• cystic fibrosis
• mutation

• Asian People
• Child
• Cystic Fibrosis/diagnosis
• Cystic Fibrosis Transmembrane Conductance Regulator/genetics
• Humans
• Ion Transport
• Mutation
• White People

• CFTR
• Chinese patient
• 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.

• CFTR
• Chinese
• Cystic fibrosis
• Genetics
• Phenotype

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant disease featured by lung cysts, spontaneous pneumothorax, fibrofolliculomas and renal tumors. The causative gene for BHDS is the folliculin (FLCN) gene and more than 200 mutations have been reported in FLCN, mostly truncating mutations. The aim of this study is to better characterize the clinical features and mutation spectrum of Chinese BHDS patients and to systematically evaluate the effects of non-truncating mutations on mRNA splicing pattern.

We enrolled 47 patients from 39 unrelated families with symptoms highly suggestive of BHDS after informed consent and detailed clinical data were collected. Exon sequencing followed by multiplex ligation-dependent probe amplification testing were applied for mutation screening. The effects of non-truncating mutations, including 15 missense mutations and 6 in-frame deletions, on mRNA splicing were investigated by minigene assays.

A total of 24 FLCN germline variants were found in 39 patients from 31 distinct families. Out of these patients, 100% (36/36) presented with lung cysts and 58.3% (21/36) had experienced spontaneous pneumothorax. Seventeen mutation carriers had skin lesions (47.2%, 17/36) and 9 (30%, 9/30) had kidney lesions including 8 with renal cysts and 1 with renal hamartoma. Among all detected variants 14 (58.3%, 14/24) were novel, including 11 variants classified to be pathogenic and 3 variants of uncertain significance. None of 21 non-truncating mutations changed the mRNA splicing pattern of minigenes.

We found different clinical features of Chinese BHDS patients compared with Caucasians, with more lung cysts and pneumothorax but fewer skin lesions and malignant renal cancer. Chinese patients with BHDS also have a different mutation spectrum from other races. Non-truncating mutations in FLCN did not disrupt mRNA splicing pattern, in turn supporting the hypothesis that these mutations impair folliculin function by disrupting the stability of the FLCN gene product.

The online version of this article (10.1186/s13023-019-1198-y) contains supplementary material, which is available to authorized users.

• Birt-Hogg-Dubé syndrome (BHDS)
• Clinical manifestations
• FLCN
• Minigene assay
• Mutation spectrum
• Non-truncating mutation

Cystic fibrosis (CF) is rare in Asian populations relative to the Caucasian population. In this paper, we report the cystic fibrosis transmembrane conductance regulator (CFTR) variation in a family of Chinese CF patients, and systematically review the previous literature.

Here we report a 30-month-old Chinese girl who was diagnosed with CF based on her history and symptoms such as recurrent productive cough, wheezing with repeated infection of Pseudomonas aeruginosa, and parasinusitis. Chest computed tomography (CT) scanning revealed obvious exudative lesions and bilateral bronchiectasis. Liver CT scanning revealed a low-density lesion in the left lobe of the liver. A diagnosis of CF was made based upon CFTR gene tests. The CFTR gene was sequenced using the blood samples of her and her parents and showed a heterozygous novel missense mutation of c.753_754delAG in exon 7. In addition, a heterozygous c.1240 C>T mutation was found in exon 10 of the CFTR. The mutation c.753_754delAG was verified to have been inherited from her mother, and the c.1240 C>T mutation was from her father who was diagnosed with congenital absence of vas deferens.

A novel mutation of CFTR, c.753_754delAG, was found in a Chinese CF child. c.2909G>A is the most common mutation among Chinese CF patients.

• Cystic fibrosis
• Cystic fibrosis transmembrane conductance regulator
• Mutation
• Chinese children
• Case report

Cystic fibrosis (CF) is a rare disease most commonly seen in Caucasians. Only a few Chinese CF patients have been described in literature, taking into account the large population of China. In this systematic review, we collected the clinical and genetic information of 71 Chinese CF patients based on all available data. Compared with Caucasians, Chinese CF patients often present atypical symptoms, mainly displaying symptoms of pulmonary infection with fewer digestive symptoms. An ethnicity-specific CFTR variant spectrum was also observed in CF patients of Chinese origin, with p.Gly970Asp as the most common mutation while p.Phe508del, the most common pathogenic mutation in CF patients of Caucasian origin, is rare, suggesting the necessity of a Chinese-specific CFTR variant screening panel. Besides, multiplex ligation-dependent probe amplification analysis should be routinely considered, especially for those with unidentified mutations. Potential under-diagnosis of CF in Chinese patients might be caused by a combination of atypical clinical features and genetic heterogeneity in Chinese CF patients, the inaccessibility of sweat and genetic testing facilities, and the one-child policy in China. With the approval of promising small molecule correctors and potentiators, molecular characterization of Chinese-specific CFTR mutations will help to realize more precise treatment for Chinese CF patients.

• CFTR
• Chinese patients
• Cystic fibrosis
• Genetics
• Phenotype