AI Article Synopsis

  • The study investigates the genetic basis of cystic fibrosis (CF)-like symptoms in 60 African patients focusing on mutations in the CFTR and ENaC genes.
  • Researchers identified three CFTR mutations (including a new one) and eight ENaC variants in patients, with specific variants linked to those showing CF-like symptoms.
  • The findings indicate that CF-like syndrome in Africa may be influenced by specific ENaC mutations, suggesting a potential complexity in CF diagnostics and treatment for affected individuals.

Article Abstract

Background: The defect in chloride and sodium transport in cystic fibrosis (CF) patients is a consequence of CF transmembrane conductance regulator (CFTR) loss of function and an abnormal interaction between CFTR and the epithelial sodium channel (ENaC). A few patients were described with CF-like symptoms, a single CFTR mutation, and an ENaC mutation.

Methods: To study African patients with CF-like symptoms and to relate the disease to gene mutations of both CFTR and ENaC genes, we collected clinical data and DNA samples from 60 African patients with a CF phenotype. The CFTR gene was first analyzed in all patients by denaturing high-performance liquid chromatography followed by direct sequencing; whereas, the sodium channel non-voltage-gated 1 alpha (SCNN1A), sodium channel non-voltage-gated 1 beta (SCNN1B), and sodium channel non-voltage-gated 1 gamma (SCNN1G) subunits of the ENaC gene were analyzed by sequencing in the five patients who carried only one CF mutation. The frequency of all identified ENaC variants was established in a control group of 200 healthy individuals and in the 55 CF-like patients without any CFTR mutation.

Results: Three CFTR mutants, including one previously undescribed missense mutation (p.A204T), and a 5T/7T variant were identified in five patients. ENaC gene sequencing in these five patients detected the following eight ENaC variants: c.72T>C and p.V573I in SCNN1A; p.V348M, p.G442V, c.1473 + 28C>T, and p.T577T in SCNN1B; and p.S212S and c.1176 + 30G>C in SCNN1G. In the 55 CF-like patients without any CFTR mutation, we identified five of these eight ENaC variants, including the frequent p.G442V polymorphism, but we did not detect the presence of the p.V348M, p.T577T, and c.1176 + 30G>C ENaC variants. Moreover, these last three ENaC variants, p.V348M, p.T577T, and c.1176 + 30G>C, were not found in the control group.

Conclusion: Our data suggest that CF-like syndrome in Africa could be associated with CFTR and ENaC mutations.

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Source
http://dx.doi.org/10.1378/chest.08-2246DOI Listing

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