ENaC subunits beta (SCNN1B) and gamma (SCNN1G) genes in 55 patients with idiopathic bronchiectasis that also lacked homozygous or compound het CFTR mutations.
Group 1 (38 patients) had sweat chloride concentration or abnormal nasal potential differences, group 2 (17 patients) were normal in both respects. Two of the group 2 patients carried the E197K variant heterozygously, and no CFTR variants. The variant was not seen in 50 ethnically matched controls.
These two were among the most severely affected in that group on pulmonary obstruction testing. The authors do not seem to conclude high penetrance for the variant, but believe it to be associated, as they conclude: “it strengthens our hypothesis that airway disease related to partly defective ENaC protein might be the result of complex susceptibility factors.”.
The authors studied SCNN1A, B, & G subunits for mutations in patients with cystic-fibrosis-like disease. In 76 patients there were 2 heterozygous for this variant. 0 out of 176 healthy controls had the variant, and 4 out of 647 controls already diagnosed with cystic fibrosis (two CFTR mutations).
The authors combine SCNN1A, B, & G variants with <2.5% minor allele frequency and find 30% of cases are carriers, while only 9% of controls and report this combined data has significance of p < 0.0001. We can use this combined data to make an extremely rough estimate of penetrance: assuming an incidence of 1 in 5,000 for cystic-fibrosis-like disease (.02%), carriers of one of these variants has a .05% attributable increased risk (total risk of .07%).