Distinct CFTR Mutation Spectrum and Atypical Clinical Presentations in Chinese Patients with Cystic Fibrosis

TL;DR

Chinese cystic fibrosis patients have unique genetic mutations and atypical symptoms, requiring tailored diagnostic and treatment approaches.

Contribution

Identifies distinct CFTR mutation patterns and atypical clinical features in Chinese CF patients, highlighting the need for localized precision medicine.

Findings

Chinese CFTR mutations differ from global patterns, with low p.Phe508del frequency and high region-specific variants.

Many Chinese CF patients present with atypical symptoms like pseudo-Bartter syndrome and vas deferens absence, not typical respiratory issues.

Current Western diagnostic pathways may not apply to Chinese patients due to these unique clinical and genetic features.

Abstract

Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and primarily affects the respiratory, digestive, and reproductive systems. Globally, CF is most prevalent among European ancestry, with an incidence rate of approximately 1/2500 to 1/3500. In China, the incidence is about 1/128,000. However, CF is not extremely rare in the Chinese population; rather, its prevalence is significantly underestimated. The CFTR mutation spectrum in China is highly unique, characterized by an extremely low frequency of p.Phe508del. Instead, region-specific mutations such as p.Gly970Asp, p.Ile1023Arg, and p.Arg553Ter predominate, alongside a high proportion of splicing variants and complex rearrangements. A significant proportion of Chinese CF patients primarily present with CF-like phenotypes within the CF-related disease spectrum (such as congenital bilateral absence of the vas deferens and pseudo-Bartter syndrome), exhibiting overlapping features with classic CF but lacking typical respiratory-dominant symptoms. This review examines how these atypical symptoms deviate from the diagnostic pathways established in Western countries. Establishing localised data and functional platforms is a prerequisite for achieving precision medicine. Achieving a transition from symptom-focused care to defect-correcting therapy will require coordinated multicenter collaboration and sustained infrastructure development.

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