Complex cystic fibrosis allele R334W-R1158X results in reduced levels of correctly processed mRNA in a pancreatic sufficient patient

Hum Mutat. 1996;8(2):134-9. doi: 10.1002/(SICI)1098-1004(1996)8:2<134::AID-HUMU5>3.0.CO;2-B.

Abstract

CFTR alleles containing two mutations have been very rarely found in cystic fibrosis (CF) patients. They provide an opportunity to study the effect of two in cis-interacting gene defects on gene expression. Here, we describe a three-generation CF family with a complex CFTR allele that has not been previously described, containing the missense mutation R334W in exon 7 and the nonsense mutation R1158X in exon 19. Lymphocyte RNA analysis showed that (1) the mRNA corresponding to the complex allele is present although at markedly reduced levels; and (2) the nonsense mutation does not lead to detectable skipping of exon 19. The clinical picture of the patients with the genotype R334W-R1158X/delta F508 is characterized by pancreatic sufficiency and an atypical course of the disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Alternative Splicing
  • Child
  • Child, Preschool
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Haplotypes
  • Humans
  • Male
  • Mutation*
  • Pancreas / physiopathology*
  • Pedigree
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism

Substances

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