ENaCβ and γ genes as modifier genes in cystic fibrosis

Abstract

Our results suggest that genetic variants in ENaCbeta and gamma genes do not modulate disease severity in the majority of CF patients.

Epithelial sodium channel (ENaC) family: Phylogeny, structure–function, tissue distribution, and associated inherited diseases

“…However, nasal potential difference measurements did not indicate a functional effect of these variants on Na + transport, at least in the nasal epithelium of these patients. Thus, the authors concluded that variants in SCNN1B and SCNN1G genes are not associated with CF severity in the cohort examined (Viel et al, 2008). …”

“…Therefore, it has been suggested that mutations in ENaC genes may be involved in some forms of cystic fibrosis. To examine the hypothesis that ENaC mutations may be associated with the degree of severity of CF, a French group screened genomic DNA of 56 CF patients for the presence of variants in SCNN1B and SCNN1G genes (Viel et al, 2008). By using denaturing high-performance liquid chromatography (DHPLC), they found 4 missense mutations in three patients out of 56 (T313M and G589S in β, and L481Q and V546I in γ subunit).…”

Could a defective epithelial sodium channel lead to bronchiectasis

“…The coding regions of ENaCβ and ENaCγ have been amplified in twelve fragments. Primer sequences have been previously described [ 17 ]. Reactions were performed in a volume of 50 μl containing 50 mM Tris-HCl (pH 8.4), 1.5 mM MgCL 2 , 200 μM of all four deoxynucleotides, 0.5 mM each of the primers, 2.5 units of Taq Polymerase (Gold, Perkin Elmer) and 100 ng template DNA.…”

Disease-modifying genes and monogenic disorders: experience in cystic fibrosis

“…Additional genes of the CFTR interactome, such as SCNN1B and SCNN1G encoding the β-subunits and γ-subunits of ENaC,78 STX1A ,79 KRT19 , PPP2R4 , PPP2R1A , and SNAP23 ,80 have been found to be involved in the modification of CF lung disease. While the modulating effect of SCNN1B and SCNN1G could not be confirmed,81 the influence of STX1A on lung disease severity was replicated in an independent CF patient cohort and variant rs2228607 was shown to reinforce aberrant splicing of STX1A mRNA, triggering nonsense-mediated mRNA decay and indicating functional relevance of this variant 79. The findings by Gisler et al80 are based upon longitudinal data for six different lung function parameters and are waiting replication; however, to have comparable longitudinal data from an independent CF patient cohort at hand is not simple.…”