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Clinical outcomes of a large cohort of individuals with the F508del/5T;TG12 CFTR genotype

      Highlights

      • Individuals with the F508del/5T;TG12 genotype needed a long-term follow-ups.
      • CF patients with the F508del/5T;TG12 genotype have a mild respiratory involvement.
      • CRMS/CFSPID with the F508del/5T;TG12 have a higher risk to disease progression.

      Abstract

      Background

      In recent years, patients with cystic fibrosis (CF) conductance regulator (CFTR) variant poly(T) sequences have been increasingly reported with a wide spectrum of clinical severity. We describe the long-term clinical outcomes and progression to a CF diagnosis over time in a large Italian cohort of patients carrying the CFTR F508del/5T;TG12 genotype.

      Methods

      A retrospective analysis of subjects from 10 CF centres in Italy with the F508del/5T;TG12 genotype was performed. Demographic, clinical, microbiological, and biochemical data, as well as information about the follow-ups and complications of the enroled patients, were collected.

      Results

      A total of 129 subjects (54 females; median age: 15.0 years, range: 0–58 years; 59 older than 18 years) were included. In terms of initial diagnoses, 30 were CF (23.3%), 41 were CFTR-related disorder (CFTR-RD) (31.7%), and 58 were CF transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID) (45.0%). After a median follow-up of 6.7 years (range 0.2–25 years), 15 patients progressed to CF, bringing the total number of CF diagnoses to 45/129 (34.9%). Most of these patients had mild lung diseases with pancreatic sufficiency and a low prevalence of CF-related complications.

      Conclusions

      At the end of the study, 34.9% of subjects with the CFTR F508del/5T;TG12 genotype were diagnosed with CF. We suggest including patients with the F508del/5T;TG12 genotype in long-term follow-ups.

      Keywords

      Abbreviations:

      CF (cystic fibrosis), CFTR (cystic fibrosis transmembrane conductance regulator), PI (pancreatic insufficiency), CFTR-RD (CFTR-related disorder), CBAVD (congenital bilateral absence of vas deferens), NBS (newborn bloodspot screening), CRMS/CFSPID (cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis), SCC (sweat chloride concentration), IRT (immunoreactive trypsinogen), MLPA (multiplex ligation-dependant probe amplification), PS (pancreatic sufficiency), FEV1 (forced expiratory volume in the 1st second), Pa (Pseudomonas aeruginosa), Br (bronchiectasis), HA (hypochloremic alkalosis), NP (nasal polyposis), Sin (sinusitis), DIOS (distal intestine obstructive syndrome)
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