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

doi:10.1016/j.jcf.2018.09.002

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.

Authors

Katherine Keenan¹, Annie Dupuis², Katherine Griffin³, Carlo Castellani⁴, Elizabeth Tullis⁵, Tanja Gonska⁶

Affiliations

¹ Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
² Clinical Research Services, The Hospital for Sick Children, Toronto, Ontario, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
³ Division of Respirology, St. Michael's Hospital, Toronto, Ontario, Canada.
⁴ Cystic Fibrosis Centre, Gaslini Institute, Genoa, Italy.
⁵ Division of Respirology, St. Michael's Hospital, Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁶ Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: tanja.gonska@sickkids.ca.

PMID: 30279124
DOI: 10.1016/j.jcf.2018.09.002

Abstract

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

Substances

Cystic Fibrosis Transmembrane Conductance Regulator