Identification of a splice site mutation (2789 +5 G > A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis

Hum Mutat. 1997;9(4):332-8. doi: 10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7.


A splicing mutation was identified at the +5 position of the splice donor site of exon 14b of CFTR in CF patients in a consanguineous family that is remarkable for unusually mild disease. Quantitative studies of nasal epithelial mRNA revealed that homozygotes for the spice site mutation produced approximately 4% of the normal amount of normally-spliced CFTR. We propose that this small amount of normally spliced mRNA is associated with synthesis of some normal CFTR protein, and accounts for the mild phenotype. Further characterization of epithelial function and clinical phenotype in patients bearing this form of mutation, termed a type V mutation, will be useful in determining the level of CFTR associated with amelioration of lung disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Chlorides / analysis
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • Epithelium
  • Exons / genetics
  • Female
  • Humans
  • Male
  • Nasal Mucosa
  • Pancreas / metabolism
  • Pedigree
  • Point Mutation / genetics*
  • RNA Splicing / genetics*
  • RNA, Messenger / genetics*
  • Sweat / chemistry


  • CFTR protein, human
  • Chlorides
  • DNA, Complementary
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator