Cystic fibrosis with non-G551D gating mutations in Italy: Epidemiology and clinical characteristics

Donatello Salvatore, Vincenzo Carnovale, Fabio Majo, Rita Padoan, Marco Salvatore, Domenica Taruscio, Annalisa Amato, Gianluca Ferrari, Giuseppe Campagna

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) gating mutations (GMs) result in CFTR that is present at the cell surface but nonfunctional. Patients with the G551D mutation, the most prevalent worldwide, have been well studied. Italian GM patients have mainly non-G551D mutations. We studied their epidemiology and clinical characteristics in the period spanning the pre/post ivacaftor introduction to the Italian market.

METHODS: Data from the Italian CF Registry were used to describe patients with GMs and compare them with F508del homozygous (F/F) patients.

RESULTS: In total, 186 patients with GMs (median [range] age, 21.96 [0.13-63.38] years) were identified among the 5552 patients included in the study (3.3%). They had lower sweat chloride values at diagnosis than the F/F and a lower ratio of males. In the GM group, examining the data of the years 2012 and 2017 and comparing with F/F, lung infection by Staphylococcus aureus and diabetes became less prevalent, and better FEV1 and nutritional status were observed in 2017. The cross-sectional evaluation year-by-year from 2012 to 2017 of the GM group showed improving trends in lung function and body mass index, and the decreasing prevalence of diabetes compared with F/F. Longitudinal evaluation of GM patients showed improvement in percent predicted (pp)FEV1 and nutrition in the 2012-2017 period. These variations correspond to the introduction of treatment with the CFTR potentiator ivacaftor (2014/2015).

CONCLUSIONS: Italian patients with GMs are few and are characterized by milder phenotypes than F/F patients. Improved outcomes are likely influenced by treatment with ivacaftor.

Original languageEnglish
Pages (from-to)442-449
Number of pages8
JournalPediatric Pulmonology
Issue number2
Publication statusPublished - Feb 2021


  • Adolescent
  • Adult
  • Aminophenols/therapeutic use
  • Body Mass Index
  • Child
  • Child, Preschool
  • Chloride Channel Agonists/therapeutic use
  • Chlorides/analysis
  • Cystic Fibrosis/drug therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  • Diabetes Mellitus/epidemiology
  • Female
  • Forced Expiratory Volume
  • Humans
  • Infant
  • Italy
  • Male
  • Middle Aged
  • Mutation
  • Quinolones/therapeutic use
  • Registries
  • Staphylococcal Infections/epidemiology
  • Sweat/chemistry
  • Young Adult


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