Intron-8 polythymidine sequence in Australasian individuals with CF mutations R117H and R117C

Eur Respir J. 2001 Jun;17(6):1195-200. doi: 10.1183/09031936.01.00057001.

Abstract

Compound heterozygotes for a severe cystic fibrosis transmembrane conductance regulator (CFTR) mutation and the R117H or R117C mutation (R117H/C) have clinical presentations that vary from classic cystic fibrosis (CF) to an incidental genetic finding. The aim of this study was to assess the influence of the intron-8 polythvmidine sequence (IVS8) on the relationship between genotype and phenotype of individuals with R117H/C. All individuals with R117H/C known to CF clinics in Australia and New Zealand were retrospectively studied by collecting information on genotype, age, pancreatic status, sweat electrolytes, sputum microbiology and pulmonary function. Forty-one individuals (39 with R117H and two with R117C), 16 on an IVS8-5T background and 25 on an IVS8-7T background were identified. Twelve individuals presented clinically, four were siblings of known R117H/C compound heterozygotes and 25 were detected by newborn screening. Eleven of 14 of the IVS8-5T group (78%) with sweat chloride results available had sweat CI > 60 mmol x L(-1) compared to 5 (20%) of the R117H/7T group (Chi-squared=10.4, p=0.001). Two were pancreatic insufficient, both IVS8-5T. Two IVS8-5T individuals have recently died (aged 43 and 19) and of the 14 surviving IVS8-5T group, 11 (79%) are symptomatic compared to eight (32%) of the IVS8-7T individuals (Chi-squared=6.1, p=0.01). In conclusion, most individuals with R117H/C on a IVS8-5T background have an elevated sweat chloride and clinical cystic fibrosis, which in some cases is severe. Most individuals with R117H/C on an IVS8-7T background do not have clinical cystic fibrosis but should be followed for the development of clinical disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Australia
  • Child
  • Child, Preschool
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / mortality
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • Genotype
  • Humans
  • Infant
  • Introns / genetics*
  • Male
  • Mutation / genetics*
  • New Zealand
  • Oceanic Ancestry Group / genetics*
  • Phenotype
  • Prognosis
  • Survival Analysis

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator