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

Am J Hum Genet. 1995 Mar;56(3):623-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Base Sequence
  • Child
  • Child, Preschool
  • Chromosome Mapping
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • DNA / analysis
  • Exons
  • Genotype
  • Humans
  • Introns
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Phenotype
  • Point Mutation*
  • RNA / analysis
  • RNA Splicing*

Substances

  • CFTR protein, human
  • Membrane Proteins
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • RNA
  • DNA

Associated data

  • GENBANK/Z34919