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

Xiaobei Guo,Keqiang Liu,Yusen Situ,Kai-Feng Xu,Xinlun Tian,Yaping Liu,Xue Zhang

doi:10.1186/s13023-018-0968-2

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.

Highlights

Cystic fibrosis (CF, OMIM # 219700) is considered to be a rare autosomal recessive disease involving multiple organs, especially the lungs and digestive organs
[1] It is a multisystem disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene located in chromosome 7, which encodes the chloride ion channel. [2, 3] Since the CFTR gene was isolated as the pathogenic gene of CF in 1989, [2, 4, 5] over 2000
Diagnosis criteria of allergic bronchopulmonary aspergillosis (ABPA) Diagnosis of Allergic bronchopulmonary aspergillosis (ABPA) was achieved according to the consensus criteria of the cystic fibrosis foundation in 2003 [12]: 1) an unexplained acute or subacute pulmonary function exacerbation; 2) a total serum Immunoglobulin E concentration greater than 1000 IU/mL, unless the patient was receiving corticosteroids; 3) an immediate cutaneous reaction to Aspergillus fumigatus or serum IgE antibody to A. fumigatus; 4) precipitating antibodies to A. fumigatus or serum IgG antibody to A. fumigatus by an in vitro test; 5) New or recent abnormalities found via chest radiography or chest CT that have not cleared with antibiotics and standard physiotherapy

Summary

Introduction

Cystic fibrosis (CF, OMIM # 219700) is considered to be a rare autosomal recessive disease involving multiple organs, especially the lungs and digestive organs. Compared with the relatively higher morbidity in Caucasians, much fewer CF patients have been reported in Asia, and the incidence varies greatly from 1:10000 to 1:40750 among different countries. Yang and colleagues enrolled 229 Chinese individuals with chronic diarrhea or chronic upper or lower respiratory infection, which are symptoms that are similar to CF, but none of the patients were detected with abnormally elevated sweat Na+. They concluded that CF might be quite rare in China. Even if CF remains a rare disease, considering the large population in China, the expected number of CF patients might be over 20,000 based on a population of 1.39 billion. Due to inadequate awareness of the disease by Chinese physicians, atypical manifestations and a different mutation spectrum compared to Caucasians, combined with the inaccessibility of sweat and genetic testing facilities, the diagnosis of CF still remains very difficult in Chinese

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Conclusion