Identification of a Novel 5' Alternative CFTR mRNA Isoform in a Patient with Nasal Polyposis and CFTR Mutations.

Human mutation

PubMedID: 24633926

Hinzpeter A, de Becdelièvre A, Bieth E, Gameiro C, Brémont F, Martin N, Costes B, Costa C, Aissat A, Lorot A, Prulière-Escabasse V, Goossens M, Fanen P, Girodon E. Identification of a Novel 5' Alternative CFTR mRNA Isoform in a Patient with Nasal Polyposis and CFTR Mutations. Hum Mutat. 2014;.
Cystic Fibrosis may be revealed by nasal polyposis (NP) starting early in life. We performed CFTR DNA and mRNA analyses in the family of a 12y-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 of 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. 5'RACE analysis showed the presence of a novel transcript, where the canonical exon 1 was replaced by an alternative exon called 1a-L (1a-Long). This case report could represent the first description of a CFTR related-disorder associated with the presence of a 5' alternative, probably non functional transcript, similar to those of fetal origin. This article is protected by copyright. All rights reserved.