c.3623G > A mutation encodes a CFTR protein with impaired channel function

Area of Science:

• Molecular biology
• Genetics
• Biochemistry

Background:

• Investigating a pediatric African-American cystic fibrosis (CF) patient with F508del and a novel c.3623G>A mutation.
• Characterizing the clinical features and molecular defects of the c.3623G>A mutation.

Observation:

• The G1208D-CFTR protein, encoded by c.3623G>A, shows moderate processing defects and impaired channel function.
• Partial rescue of G1208D-CFTR function was observed with VX-809 and low-temperature incubation (28°C).
• The patient presented with mild clinical manifestations of CF disease.

Findings:

• The c.3623G>A mutation results in a CFTR protein with reduced expression and impaired ion channel activity.
• Biochemical analysis revealed moderate processing defects and functional deficits in the G1208D-CFTR variant.
• The patient's mild phenotype correlates with the characterized molecular defect.

Implications:

• The c.3623G>A mutation is identified as a CF-causing mutation, expanding the spectrum of known CFTR variants.
• This research enhances understanding of rare CFTR mutations in minority populations.
• Findings support personalized therapeutic strategies for CF patients with rare mutations.