title: Identification of a novel 5' alternative CFTR mRNA isoform in a patient with nasal polyposis and CFTR mutations.
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.
authors.affiliation: INSERM U955, Créteil, France; Université Paris-Est, Créteil, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hinzpeter
authors.forename: Alix
authors.initials: A
authors.lastname: de Becdelièvre
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.forename: Christine
authors.initials: C
authors.lastname: Gameiro
authors.forename: François
authors.initials: F
authors.lastname: Brémont
authors.forename: Natacha
authors.initials: N
authors.lastname: Martin
authors.forename: Bruno
authors.initials: B
authors.lastname: Costes
authors.forename: Catherine
authors.initials: C
authors.lastname: Costa
authors.forename: Abdel
authors.initials: A
authors.lastname: Aissat
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lorot
authors.forename: Virginie
authors.initials: V
authors.lastname: Prulière-Escabasse
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.forename: Pascale
authors.initials: P
authors.lastname: Fanen
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Girodon
mesh_terms: D020121:5' Untranslated Regions; D017398:Alternative Splicing; D002648:Child; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D023061:Gene Order; D006801:Humans; D008297:Male; D009154:Mutation; D009298:Nasal Polyps / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D059368:RNA Isoforms; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D059368:RNA Isoforms; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: CFTR; alternative transcripts; cystic fibrosis; nasal polyposis; transcription regulation