Genetic Heterogeneity Correlated with Phenotypic Variability in 48 Patients with Cystic Fibrosis

Area of Science:

• Medical Genetics
• Molecular Biology

Background:

• Cystic fibrosis (CF) is a severe autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
• CFTR mutation spectrum and frequency vary geographically, necessitating regional genetic studies.
• Understanding CFTR variants is key to diagnosing and managing CF patients.

Purpose of the Study:

• To identify CFTR genetic variants in 48 CF patients from Romania's Moldova region.
• To establish genotype-phenotype correlations in this patient cohort.
• To compare findings with existing literature and highlight regional particularities.

Main Methods:

• Retrospective analysis of CF patient data.
• Initial screening for 38 common CFTR mutations.
• Next-generation sequencing (NGS) for comprehensive CFTR gene analysis in specific cases.

Main Results:

• F508del was the most prevalent CFTR variant (69.79%), found in homozygous and compound heterozygous forms.
• New CFTR variants (e.g., R1158X, K598*) were identified in the Romanian population.
• More severe CF phenotypes correlated with CFTR classes I, II, III, and VII mutations; respiratory and gastrointestinal issues were common.

Conclusions:

• Genotype-phenotype correlations in Romanian CF patients align with general literature but show regional specifics.
• Early diagnosis via genetic testing enables personalized CF management.
• Identification of novel CFTR variants and carrier screening are vital for genetic counseling and prenatal diagnosis.