Which CFTR allele is associated with an increased susceptibility to cystic fibrosis in homozygotes?

• A. G542X
• B. ΔF508
• C. Both G542X and ΔF508
• D. None of the above

Answer: (B)

The choice of ΔF508 as the CFTR allele associated with an increased susceptibility to cystic fibrosis in homozygotes is based on its well-established role in the disease's pathogenesis. ΔF508 is a deletion mutation that removes a single phenylalanine residue at position 508 of the CFTR protein. This alteration leads to improper folding of the CFTR protein, resulting in its degradation before it reaches the cell surface. Individuals who are homozygous for this allele exhibit severe manifestations of cystic fibrosis due to the significant reduction in functional CFTR protein, which is crucial for chloride ion transport across epithelial membranes.

In terms of disease severity, homozygosity for ΔF508 correlates strongly with the classic symptoms of cystic fibrosis, including respiratory and digestive complications. Although G542X is also a CFTR mutation, which introduces a premature stop codon and leads to nonfunctional CFTR protein, ΔF508 mutations are more common and recognized as presenting a greater risk when homozygous, hence highlighting its particular clinical relevance in cystic fibrosis cases.