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

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.

• Authors: Antonella Tosco, Alice Castaldo, Carla Colombo, Laura Claut, Vincenzo Carnovale, Paola Iacotucci, Marco Lucarelli, Giuseppe Cimino, Benedetta Fabrizzi, Nicole Caporelli, Fabio Majo, Fabiana Ciciriello, Rita Padoan, Piercarlo Poli, Giovanni Taccetti, Claudia Centrone, Rosaria Casciaro, Carlo Castellani, Donatello Salvatore, Carmela Colangelo, Paolo Bonomi, Giuseppe Castaldo, Vito Terlizzi
• Journal: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society (J Cyst Fibros) Vol. 21 Issue 5 Pg. 850-855 (09 2022) ISSN: 1873-5010 [Electronic] Netherlands
• PMID: 35523714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Chemical References

• CFTR protein, human
• Cystic Fibrosis Transmembrane Conductance Regulator

Topics

• Adolescent
• Cohort Studies
• Cystic Fibrosis (diagnosis, epidemiology, genetics)
• Cystic Fibrosis Transmembrane Conductance Regulator (genetics, metabolism)
• Female
• Genotype
• Humans
• Mutation
• Retrospective Studies