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Identification of a Novel 5′ Alternative CFTR m RNA Isoform in a Patient with Nasal Polyposis and CFTR Mutations
Author(s) -
Hinzpeter Alexandre,
Becdelièvre Alix,
Bieth Eric,
Gameiro Christine,
Brémont François,
Martin Natacha,
Costes Bruno,
Costa Catherine,
Aissat Abdel,
Lorot Aurélie,
PrulièreEscabasse Virginie,
Goossens Michel,
Fanen Pascale,
Girodon Emmanuelle
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22548
Subject(s) - exon , biology , cystic fibrosis transmembrane conductance regulator , cystic fibrosis , messenger rna , microbiology and biotechnology , gene isoform , complementary dna , alternative splicing , mutation , genetics , gene
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.