Nasal potential difference in suspected cystic fibrosis patients with 5T polymorphism.


Journal

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966

Informations de publication

Date de publication:
07 2020
Historique:
received: 30 03 2019
revised: 05 07 2019
accepted: 06 07 2019
pubmed: 25 7 2019
medline: 14 9 2021
entrez: 24 7 2019
Statut: ppublish

Résumé

5T polymorphism is a CFTR mutation with unclear clinical consequences: the phenotype varies from healthy individuals to Cystic Fibrosis (CF). The aim of this study was to evaluate if nasal potential difference (NPD) and sweat testing correlate with symptoms and CF diagnosis in 5T patients. 86 patients with 5T who had undergone NPD measurement, were included (6 homozygous (5T/5T), 41 with a PI-CF causing mutation in trans (5T/PI-CF), 11 with a PS-CF causing mutation in trans (5T/PS-CF) and 28 without a known mutation in trans (5T/?). Data including age, phenotype, sweat chloride and follow up were collected. 33% of the 5T/5T patients had abnormal NPD results, compared to 70% in 5T/PI-CF; 33% in 5T/PS-CF and 29% in 5T/?. The percentage of high or borderline sweat chloride was highest in 5T/PI-CF, and 5T/?, compared to 5T/5T and 5T/PS-CF (91, 96, 80, and 63%, respectively). TGm (number of TG repeats in intron 8) analysis was performed in 21 5T/PI-CF patients. TG11 was associated with lower sweat chloride, lower percentage of abnormal NPD and less progression of symptoms compared to TG12 and TG13. There is much variation in clinical status among 5T patients. All patients in this study with 5T/PS CF, all patients with both normal NPD and sweat test, and most patients with TG11 were stable or improving over time. Therefore, NPD measurement and TGm status aid to assess if a patient is at high risk for developing CF or CFTR-related disease and if specific follow up in a CF center is required.

Sections du résumé

BACKGROUND
5T polymorphism is a CFTR mutation with unclear clinical consequences: the phenotype varies from healthy individuals to Cystic Fibrosis (CF). The aim of this study was to evaluate if nasal potential difference (NPD) and sweat testing correlate with symptoms and CF diagnosis in 5T patients.
METHODS
86 patients with 5T who had undergone NPD measurement, were included (6 homozygous (5T/5T), 41 with a PI-CF causing mutation in trans (5T/PI-CF), 11 with a PS-CF causing mutation in trans (5T/PS-CF) and 28 without a known mutation in trans (5T/?). Data including age, phenotype, sweat chloride and follow up were collected.
RESULTS
33% of the 5T/5T patients had abnormal NPD results, compared to 70% in 5T/PI-CF; 33% in 5T/PS-CF and 29% in 5T/?. The percentage of high or borderline sweat chloride was highest in 5T/PI-CF, and 5T/?, compared to 5T/5T and 5T/PS-CF (91, 96, 80, and 63%, respectively). TGm (number of TG repeats in intron 8) analysis was performed in 21 5T/PI-CF patients. TG11 was associated with lower sweat chloride, lower percentage of abnormal NPD and less progression of symptoms compared to TG12 and TG13.
CONCLUSION
There is much variation in clinical status among 5T patients. All patients in this study with 5T/PS CF, all patients with both normal NPD and sweat test, and most patients with TG11 were stable or improving over time. Therefore, NPD measurement and TGm status aid to assess if a patient is at high risk for developing CF or CFTR-related disease and if specific follow up in a CF center is required.

Identifiants

pubmed: 31331863
pii: S1569-1993(19)30822-7
doi: 10.1016/j.jcf.2019.07.001
pii:
doi:

Substances chimiques

Chlorides 0
Cystic Fibrosis Transmembrane Conductance Regulator 126880-72-6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

627-631

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2019 European Cystic Fibrosis Society. All rights reserved.

Auteurs

Bente L Aalbers (BL)

Department of Pulmonology, University Medical Center Utrecht, Postbus 85500, 3508, GA, Utrecht, the Netherlands. Electronic address: b.l.aalbers-2@umcutrecht.nl.

Yasmin Yaakov (Y)

Pediatric Gastroenterology Unit and Cystic Fibrosis Center, Hadassah-Hebrew University Medical Center, Kiryat Hadassah, POB 12000, Jerusalem 91120, Israel.

Nico Derichs (N)

CF Center, Pediatric Pulmonology and Immunology, Charité Universitätsmedizin, Charitépl. 1, 10117 Berlin, Germany.

Nicholas J Simmonds (NJ)

Department of Cystic Fibrosis, Royal Brompton Hospital and Imperial College, Sydney Street, SW3 6NP London, United Kingdom.

Elke De Wachter (E)

Department of Pediatric Pneumology, UZ Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium.

Paola Melotti (P)

Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata. Piazzale Aristide Stefani 1, 37126 Verona, Italy.

Kris De Boeck (K)

Department of Pediatric Pulmonology, University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium.

Teresinha Leal (T)

Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Place de l'Université 1, B-1348 Louvain-la-Neuve, Brussels, Belgium.

Burkhart Tümmler (B)

CF Center and Clinical Research Group, Department of Pediatric Pneumology and Neonatology, OE 6710, Medical School Hannover, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.

Michael Wilschanski (M)

Pediatric Gastroenterology Unit and Cystic Fibrosis Center, Hadassah-Hebrew University Medical Center, Kiryat Hadassah, POB 12000, Jerusalem 91120, Israel.

Inez Bronsveld (I)

Department of Pulmonology, University Medical Center Utrecht, Postbus 85500, 3508, GA, Utrecht, the Netherlands.

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