title: A novel donor splice site in intron 11 of the CFTR gene, created by mutation 1811+1.6kbA-->G, produces a new exon: high frequency in Spanish cystic fibrosis chromosomes and association with severe phenotype.
abstract: mRNA analysis of the cystic fibrosis transmembrane regulator (CFTR) gene in tissues of cystic fibrosis (CF) patients has allowed us to detect a cryptic exon. The new exon involves 49 base pairs between exons 11 and 12 and is due to a point mutation (1811+1.6kbA-->G) that creates a new donor splice site in intron 11. Semiquantitative mRNA analysis showed that 1811+1.6kbA-->G-mRNA was 5-10-fold less abundant than delta F508 mRNA. Mutation 1811+1.6kbA-->G was found in 21 Spanish and 1 German CF chromosomes, making it the fourth-most-frequent mutation (2%) in the Spanish population. Individuals with genotype delta F508/1811+1.6kbA-->G have only 1%-3% of normal CFTR mRNA. This loss of 97% of normal CFTR mRNA must be responsible for the pancreatic insufficiency and for the severe CF phenotype in these patients.
authors.affiliation: Molecular Genetics Department, Cancer Research Institute, Hospital Duran i Reynals, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Chillón
authors.forename: T
authors.initials: T
authors.lastname: Dörk
authors.forename: T
authors.initials: T
authors.lastname: Casals
authors.forename: J
authors.initials: J
authors.lastname: Giménez
authors.forename: N
authors.initials: N
authors.lastname: Fonknechten
authors.forename: K
authors.initials: K
authors.lastname: Will
authors.forename: D
authors.initials: D
authors.lastname: Ramos
authors.forename: V
authors.initials: V
authors.lastname: Nunes
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA / Q000032:analysis; D005091:Exons; D005838:Genotype; D006801:Humans; D007438:Introns; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D012313:RNA / Q000032:analysis; D012326:RNA Splicing
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012313:RNA; D004247:DNA