Phenotypic spectrum of patients with cystic fibrosis and cystic fibrosis-related disease carrying p.Arg117His

J Cyst Fibros. 2019 Mar;18(2):265-270. doi: 10.1016/j.jcf.2018.09.002. Epub 2018 Sep 29.


Background: The "mild" gene variant, p.Arg117His in cystic fibrosis (CF) results in highly variable phenotypes ranging from male infertility to severe lung disease. Due to current interest to include this group in CFTR-targeted therapies, this study aims to describe the disease spectrum.

Methods: Retrospective study of Toronto CF and CFTR-related p.Arg117His patients. Longitudinally captured clinical data were compared between patients with 5T/7T-variants and those with a CF or CFTR-related diagnosis. Comparison was made between p.Arg117His adults and infants identified through CF newborn screening (NBS).

Results: Twenty of fifty patients carried the 5T variant, all with a diagnosis of CF (p.Arg117His-5TCF), and 30/50 carried 7T, 7 diagnosed with CF (p.Arg117His-7TCF) and 23 with a CFTR-related disorder (p.Arg117His-7TCFTR). For those with chest HRCT results available, 75% p.Arg117His-5TCF, 33% p.Arg117His-7TCF and 27% p.Arg117His-7TCFTR patients had bronchiectasis. Further, 79% p.Arg117His-5T, 29% p.Arg117His-7TCF and 13% p.Arg117His-7TCFTR had abnormal lung function. Of those, 80% grew CF-related pathogens on respiratory culture. Interestingly, the mean maximum sweat chloride and the percentage of patients growing CF-related bacterial pathogens were identical in p.Arg117His-7 TCFTR adults and p.Arg117His infants.

Conclusions: Generally, p.Arg117His-5T patients had more severe CF disease. However, a subset of p.Arg117His-7 T patients demonstrated equally severe disease, thus warranting clinical monitoring of all p.Arg117His patients including p.Arg117His infants identified via NBS.

Keywords: CFTR-related disease; Cystic fibrosis; Cystic fibrosis newborn screening; Diagnosis; P.Arg117His.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Bronchiectasis* / diagnosis
  • Bronchiectasis* / epidemiology
  • Bronchiectasis* / etiology
  • Canada / epidemiology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / epidemiology
  • Cystic Fibrosis* / genetics
  • Cystic Fibrosis* / therapy
  • Female
  • Genetic Association Studies*
  • Genetic Variation
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Neonatal Screening / methods
  • Respiratory Function Tests / statistics & numerical data
  • Severity of Illness Index


  • Cystic Fibrosis Transmembrane Conductance Regulator