CFTR gene variants, epidemiology and molecular pathology

Area of Science:

• Genetics
• Molecular Biology
• Pediatrics

Background:

• Pathogenic variants of the CFTR gene cause a spectrum of exocrine tissue malfunctions inherited in an autosomal recessive manner.
• Over 2,000 CFTR variants exist, impacting gene and protein function differently.
• Severe variants link to typical cystic fibrosis, while mild variants cause CFTR-related disorders.

Purpose of the Study:

• To review the global and French epidemiology of CFTR variants.
• To describe the functional classification of CFTR variants.
• To illustrate molecular pathology using common CFTR variants and provide nomenclature recommendations for genetic counseling.

Main Methods:

• Literature review of CFTR variant epidemiology and classification.
• Analysis of genotype-phenotype correlations.
• Case examples of frequent CFTR variants.

Main Results:

• CFTR variants exhibit diverse effects on gene and protein function.
• A correlation exists between variant severity and disease presentation (cystic fibrosis vs. CFTR-related disorders).
• Interpretation of rare CFTR variants remains a challenge.

Conclusions:

• Understanding CFTR variant epidemiology and functional classification is crucial.
• Accurate nomenclature and classification aid genetic counseling for CFTR-related conditions.
• Further research is needed for rare variant interpretation.