Lung disease associated with the IVS8 5T allele of the CFTR gene

Am J Respir Crit Care Med. 2000 Nov;162(5):1919-24. doi: 10.1164/ajrccm.162.5.2003160.


Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. The 5T allele in intron 8 (IVS8) causes abnormal splicing in the CFTR gene, and is associated with lung disease when it occurs in cis with a missense mutation in the CFTR gene, R117H. However, the 5T variant alone has not been reported to cause lung disease. We describe two adult female patients with CF-like lung disease associated with the 5T allele. One patient's genotype is 5T-TG12-M470V/5T-TG12-M470V, and the other is DeltaF508/5T-TG12-M470V; full sequencing of the CFTR gene revealed no other mutation on the same allele as the 5T variant. The levels of full-length CFTR mRNA in respiratory epithelia were very low in these patients (11 and 6%, respectively, of total CFTR mRNA expression). Both patients had defective CFTR-mediated chloride conductance in the sweat ductal and/or acinar epithelia (sweat chloride, mmol/L, mean +/- SEM: 40.0 +/- 5.0 [n = 8 samples] and 80. 0 +/- 3.5 [n = 6 samples]) and airway epithelia (mV, mean +/- SEM CFTR-mediated Cl(-) conductance of 1.2 +/- 2.2 [n = 5 studies] and -6.75 +/- 8.1 [n = 4 studies]). These data suggest that the 5T polythymidine tract sequence on specific haplotype backgrounds (TG12 and M470V) may cause a low level of full-length functional CFTR protein and CF-like lung disease.

Publication types

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

MeSH terms

  • Age of Onset
  • Alleles*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Epithelium / metabolism
  • Female
  • Genotype
  • Haplotypes
  • Heterozygote
  • Homozygote
  • Humans
  • Introns
  • Ion Transport
  • Lung Diseases / genetics*
  • Middle Aged
  • Mutation, Missense
  • Polymorphism, Genetic
  • RNA, Messenger / analysis
  • Respiratory Mucosa / metabolism
  • Sweat / chemistry
  • Sweat / metabolism


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