[CFTR gene variations and phenotypes in seven children]

Area of Science:

• Genetics
• Pediatrics
• Molecular Biology

Background:

• Cystic fibrosis transmembrane conductance regulator (CFTR) gene variations are linked to various clinical presentations.
• Understanding genotype-phenotype correlations is essential for accurate diagnosis and management of CFTR-related disorders.
• Limited data exists on CFTR gene variations and associated phenotypes in the Chinese pediatric population.

Purpose of the Study:

• To investigate the spectrum of CFTR gene variations and their corresponding phenotypes in a cohort of Chinese children.
• To identify novel CFTR gene variations and assess their clinical significance.
• To differentiate between cystic fibrosis (CF) and CFTR-related disease (CFTR-RD) based on genetic and clinical findings.

Main Methods:

• Retrospective analysis of clinical data from 7 Chinese children with confirmed CFTR gene variations.
• Whole exome sequencing and Sanger sequencing were employed for comprehensive genetic analysis.
• Clinical manifestations, diagnostic criteria, and treatment outcomes were systematically reviewed.

Main Results:

• Fifteen CFTR gene variations were identified, including three novel variants and seven missense mutations.
• Four children were diagnosed with cystic fibrosis (CF), while three were diagnosed with CFTR-related disease (CFTR-RD).
• CFTR-RD patients exhibited milder pancreatic insufficiency and lung disease compared to CF patients; six children showed clinical improvement after treatment.

Conclusions:

• CFTR gene variants present a wide range of loci and phenotypes, with some variations of unclear pathogenicity.
• Whole exome sequencing is effective in identifying CF and CFTR-RD-causing variations.
• Timely genetic evaluation for CFTR-RD is recommended for cases not fitting typical CF criteria to ensure appropriate long-term management.