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

Katherine Keenan, Annie Dupuis, Katherine Griffin, Carlo Castellani, Elizabeth Tullis, Tanja Gonska

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)265-270
Number of pages6
JournalJournal of Cystic Fibrosis
Issue number2
Publication statusPublished - Mar 2019


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