Identification of a Novel 5′ AlternativeCFTRmRNA Isoform in a Patient with Nasal Polyposis andCFTRMutations

Abstract

Cystic fibrosis may be revealed by nasal polyposis (NP) starting early in life. We performed cystic fibrosis transmembrane conductance regulator (CFTR) DNA and mRNA analyses in the family of a 12‐year‐old boy presenting with NP and a normal sweat test. Routine DNA analysis only showed the heterozygous c.2551C>T (p.Arg851*) mutation in the child and the father. mRNA analysis showed partial exon skipping due to c.2551C>T and a significant increase in total CFTR mRNA in the patient and the mother, which was attributable to the heterozygous c. −2954G>A variant in the distant promoter region, as demonstrated by in vitro luciferase assays. The 5′ rapid amplification of cDNA ends analysis showed the presence of a novel transcript, where the canonical exon 1 was replaced by an alternative exon called 1a‐Long. This case report could represent the first description of a CFTR‐related disorder associated with the presence of a 5′ alternative, probably nonfunctional transcript, similar to those of fetal origin.

S100a9 might act as a modulator of the Toll-like receptor 4 transduction pathway in chronic rhinosinusitis with nasal polyps

“…Young's syndrome, also named sinusitis-infertility syndrome, is a rare and inherited syndrome characterized by chronic sinusitis, bronchiectasis, and decreased fertility due to azoospermia. Various studies have suggested that mutation in the Cftr gene may be involved in the pathogenesis of CRS as well as Young's syndrome 39 – 42 . Furthermore, a previous study suggested that the up-regulation of a member of matrix metalloproteinase, namely disintegrin and metalloproteinase (ADAM)-33 protein, is associated with the pathogenesis of nasal polyps 43 .…”