Identification of a Novel 5′ Alternative CFTR m RNA Isoform in a Patient with Nasal Polyposis and CFTR Mutations

Cystic fibrosis may be revealed by nasal polyposis ( NP ) starting early in life. We performed cystic fibrosis transmembrane conductance regulator ( CFTR ) DNA and m RNA 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.2551 C > T (p. A rg851*) mutation in the child and the father. m RNA analysis showed partial exon skipping due to c.2551 C > T and a significant increase in total CFTR m RNA in the patient and the mother, which was attributable to the heterozygous c. −2954 G > 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‐ L ong. 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.