Clinical and genetic characteristics of cystic fibrosis in CHINESE patients: a systemic review of reported cases

Abstract

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.

The novel mutation c.1210-3C>G in cis with a poly-T tract of 5T affects CFTR mRNA splicing in a Chinese patient with cystic fibrosis

“…In contrast, the morbidity of CF is low in China, given that there are considerably fewer reports of CF among large populations of Chinese. Atypical clinical syndromes and novel mutations unidentified previously in Caucasians also show an ethnicity-specific pattern in Chinese CF patients [9]. In this study, we aimed to identify potential pathogenic mutations in a CF patient of Chinese origin.…”

“…In Amato's report, p.Gly970Asp mutant plasmidtransfected HEK293 cells showed very low channel activity, demonstrating the mutation's pathogenicity [14]. In addition, with an allele frequency of 9.8%, p.Gly970Asp is the most commonly seen hotspot mutation in CF patients of Chinese origin [9]. This may encourage the eligibility of pharmaco-gene treatment focusing on p.Gly970Asp in order to correct the CF phenotype in Chinese patients.…”

“…All 27 coding exons were amplified and sequenced for the patient and his parents, and the results showed that the patient carried two suspected pathogenic variants ( Fig. 2A, B), c.2090G>A and c.1210-3C>G. c.2909G>A in exon 18 (p.Gly970Asp) from his mother is considered the most frequent CFTR mutation among Chinese CF patients [9]. Interestingly, the other novel variant c.1210-3C>G in intron 9, inherited from his father, is just 3 bp upstream a poly-thymine (T) sequence of 5T on the same allele.…”

“…In contrast, mutations detected in Chinese CF patients tend to be unusual among the Caucasian population [7,8]. As far as it is known, c.2909G>A in exon 18 (p.Gly970Asp, in short, G970D) of CFTR, which is restricted to Chinese CF patients and has a frequency of 9.8% (12 in 122 Chinese CF patients), becomes the most common variant [7,9]. All these facts imply that Chinese populations may have a specific CF mutation spectrum.…”

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

“…By comparison, only approximately 70 Chinese patients have been reported in the literature. [1] It was believed that CF is extremely rare in the Chinese population; however, more than half of these Chinese patients have been reported in the most recent four or five years, [2][3][4][5][6] suggesting that there might be a significant under-estimation of CF incidence in China.…”