CFTR-France: a patient-related database integrating sequence variations, genotypes and phenotypes stored in diagnostic laboratories specialized in the analysis of CFTR variation

CFTR-France has been developed since 2012 with the aim to collect, store and process any category of variants identified in the CFTR gene, thanks to the collaboration of 10 French laboratories with high expertise in the molecular analyses of this gene and the financial support of the parents’ association Vaincre la Mucoviscidose.
Since 2013, CFTR-France has been collaborating with the French Clinical Registry of patients affected with cystic fibrosis, via the association Vaincre la Mucoviscidose.
CFTR-France is a 'LSDB' (Locus Specific DataBase) dedicated to sequence variations of the CFTR gene associated with diverse clinical phenotypes, the most severe of which is Cystic Fibrosis (CF, OMIM #219700). CF is the most common life-shortening inherited autosomal recessive disorder in populations of European descent.

The specificity of CFTR-France is to compile any category of variations (disease-causing, non disease-causing and variants of unknown clinical significance) that have been identified by nine specialized laboratories in the following situations:

• Patients affected with cystic fibrosis (CF)
• Patients presenting milder phenotypes named CFTR-related disorders (CFTR-RD)
• Fetuses with abnormal ultrasonography (echogenic bowel, …)
• Newborns with pending or inconclusive diagnosis
• Asymptomatic individuals carrying at least one sequence variation on each CFTR gene (i.e. carrying two variations in trans).

The database includes the main clinical data of these individuals, genetic information from familial segregation studies, and, various variant annotations (frequency in patient and control populations, sequence homology, predicted or experimentally assessed functional impact, etc), allowing the analysis of genotype/phenotype relationships.
CFTR-France is meant to be a source of information on rare CFTR variants, regularly updated, and to contribute to a better knowledge on their clinical significance. The project consists in:

• Collecting (retrospectively) genetic data from nine French laboratories that are recognized as experts with the CFTR genetic diagnosis,
• Performing regular review of epidemiological data, experimental data, literature, and central databases on CFTR variations,
• Performing research on the clinical and functional impact of CFTR variants.

CFTR-France is not intended to allow direct submission of variants.

Coordinating Team

• Directors of the project: Pr. Mireille CLAUSTRES and Dr. Caroline RAYNAL
• Software developers: Dr. Corinne BAREIL and Dr. Souphatta SASORITH
• Data curators: Dr. Souphatta SASORITH, Dr. Corinne BAREIL, Dr. Anne BERGOUGNOUX and Dr. Caroline RAYNAL

The coordinating team in Montpellier assumes the following tasks:

• To develop electronic formats for data submission by collaborators,
• To collect, reformat, treat and curate data sent by the laboratories,
• To create appropriate bioinformatics tools for storage, analysis and retrieval,
• To implement the database infrastructure,
• To update the database contents (approximately four times/year),
• To retrieve, on request, all data on a variant identified in problematic diagnosis situations e.g. fetal suspicion of CF, genetic counseling for couples [data restricted to the French network of diagnostic laboratories],
• To organize each year a workshop bringing together the laboratories participating to CFTR-France database, representatives of the parents’ association 'Vaincre la Mucoviscidose', and representatives of the French Clinical CF Registry. The achievements of the year are presented by the coordinating team,
• To write the annual meeting report, which is available to all partners.

Board of Collaborators

The Board of Collaborators includes the laboratories who accepted to contribute and share genetic or clinical data and to bring their experience and expertise. Its task is to contribute and take decisions about future developments and orientations of the database, research projects and collaborative works to solve difficulties in the interpretation of CFTR genetic variations.

Database curation

The CFTR-France was created in 2008 at Montpellier University by Mireille CLAUSTRES, Corinne BA REIL, Marie Des GEORGES, Corinne THEZE and Caroline RAYNAL [IURC, Institut Universitaire de Recherche Clinique, Inserm U827].
It is now maintained by Corinne BAREIL, Souphatta SASORITH, Anne BERGOUGNOUX, Caroline RAYNAL and Mireille CLAUSTRES [IURC, Institut Universitaire de Recherche Clinique, PhyMedExp INSERM U1046, CNRS UMR 9214].
The curation of the database is partially funded by "Vaincre la Mucoviscidose".
The conception of the software and the bioinformatics management of the database are not funded by external grants.

CFTR-France constitutes the intellectual property of the director and curators of the database. Any unauthorized copying, storage or distribution of this material without written permission from the curators would lead to copyright and database right infringement with possible ensuing litigation. Copyright © 2017. All rights reserved. For further details, please refer to Directive 96/9/EC of the European Parliament and of the Council of March 11 (1996) on the legal protection of databases.

The public information provided by CFTR-France is for scientific purposes only, not for clinical usage. Whilst CFTR-France exercises all reasonable care to ensure that the database and data contained therein are of high quality, it makes no warranty, expressed or implied, as to the accuracy or completeness thereof or that this database or the data contained therein, is fit for a particular purpose such as the diagnosis, genetic counseling and treatment of patients. The Directors, Curators and Collaborators cannot be held responsible for any consequences arising out of any inaccuracies, omissions or misusages.

Citing CFTR-France:

Claustres M, Thèze C, des Georges M, Baux D, Girodon E, Bienvenu T, Audrezet MP, Dugueperoux I, Férec C, Lalau G, Pagin A, Kitzis A, Thoreau V, Gaston V, Bieth E, Malinge MC, Reboul MP, Fergelot P, Lemonnier L, Mekki C, Fanen P, Bergougnoux A, Sasorith S, Raynal C, Bareil C.
CFTR-France, a national relational patient database for sharing genetic and phenotypic data associated with rare CFTR variants.
Hum Mutat. 2017 Oct;38(10):1297-1315. doi: 10.1002/humu.23276. PMID: 28603918

References related to CFTR-France:

Bergougnoux A, Taulan-Cadars M, Claustres M, Raynal C.
Current and future molecular approaches in the diagnosis of cystic fibrosis.
Expert Rev Respir Med. 2018 May;12(5):415-426. doi: 10.1080/17476348.2018.1457438. PMID: 29580110

Atelier sur le Diagnostic Moléculaire de la Mucoviscidose (13-15 September 2018, Baillargues)

• Atelier: CFTR-France : banque de données dédiée aux variants rares du gène CFTR (Corinne BAREIL)

Email

Corinne BAREIL or Souphatta SASORITH

Postal address

Laboratoire de Génétique Moléculaire, CHU de Montpellier
PhyMedExp INSERM U1046, CNRS UMR 9214
IURC (Institut Universitaire de Recherche Clinique)
640 avenue du Doyen Gaston Giraud
34093 MONTPELLIER
FRANCE