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Recommendations for the classification of diseases as CFTR-related disorders

Journal of Cystic Fibrosis, Volume 10, Supplement 2, July 2011, pS86-S102

Abstract

Several diseases have been clinically or genetically related to cystic fibrosis (CF), but a consensus definition is lacking. Here, we present a proposal for consensus guidelines on cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (CFTR-RDs), reached after expert discussion and two dedicated workshops.

A CFTR-RD may be defined as “a clinical entity associated with CFTR dysfunction that does not fulfil diagnostic criteria for CF”.

The utility of sweat testing, mutation analysis, nasal potential difference, and/or intestinal current measurement for the differential diagnosis of CF and CFTR-RD is discussed. Algorithms which use genetic and functional diagnostic tests to distinguish CF and CFTR-RDs are presented.

According to present knowledge, congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis and disseminated bronchiectasis, all with CFTR dysfunction, are CFTR-RDs.

Keywords: CFTR-related disorders, CBAVD (Congenital Bilateral Absence of Vas Deferens), Pancreatitis, Bronchiectasis, Functional tests, NPD (Nasal Potential Difference), ICM (Intestinal Current Measurement).

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Footnotes

a Department of life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Verona 37134, Italy

b Laboratoire de Génétique Moléculaire, CHU Montpellier and INSERM U827, IURC Montpellier, France

c Department of Pediatrics – Pediatric Pulmonology, University Hospital, Leuven, Belgium

d CF Centre, Medizinische Hochschule Hannover, Germany

e Department of Child Health, University of Wales Swansea, Singleton Hospital, Swansea SA2 8QA, UK

f APHP, Groupe Hospitalier Henri Mondor, Service de Biochimie-Génétique and INSERM U955 Equipe 11, Créteil, France

g Pole de Pédiatrie Multidisciplinaire, Hôpital Necker, Université René Descartes, 75015 Paris, France

h Regional Molecular Genetics Service – Genetic Medicine, St. Mary's Hospital, Manchester, UK

i Department of Medical Genetics, Athens University, St Sophia's Children's Hospital, Athens, Greece

j Pediatric Gastroenterology Unit and Cystic Fibrosis Center, Hadassah University Hospital, Jerusalem, Israel

k Royal Brompton Hospital, Sydney Street, London, UK

l Verona Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy

m Department of Human Genetics, Katholieke Universiteit Leuven, Gasthuisberg O&N 1 (602), B-3000, Leuven, Belgium

n McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

o Department of Pediatrics, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, CZ 150 06, Czech Republic

p Department of Pediatrics and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

q School of Medicine, Dentistry and Biomédical Sciences, Queen's University of Belfast, Belfast, BT7 INN, Northern Ireland, UK

r Divisions of Urology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

s Department of Genetics, The Life Sciences Institute, Givat Ram Campus, The Hebrew University, Jerusalem 91904, Israel

t Department of Pediatrics and Pediatric Pulmonology, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel

u Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

v Department of Biology and Medical Genetics, Charles University, Second Faculty of Medicine and University Hospital Motol, Prague, CZ 150 06, Czech Republic

w CF Center, Department of Pediatric Gastroenterology and Nutrition, University Hospital Robert Debré, AP-HP 48, 75019 Paris, France

x Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia

y Laboratorio di Genética Medica, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlínica, Milano, Italy

z School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK

aa Institute of Child Health, University of Liverpool, Alder Hey Children's Hospital, Liverpool, L12 2AP, UK

ab Institute of Human Genetics, Medical School Hannover, Hannover, Germany

ac Adult Cystic Fibrosis Centre, St Michael's Hospital, and Division of Respirology Department of Medicine, University of Toronto, Ontario, Canada

ad Genetics and Genomics Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

ae Génétique Moléculaire et Génétique Epidémiologique INSERM U613 Laboratoire de Génétique Moléculaire et d'Histocompatibilité CHU de Brest, F-29609, Brest, France

* Corresponding author: Claude Ferec, MD, PhD, Professor of Molecular Genetics, Laboratory of Molecular Genetics, 46 rue Felix Le Dantec, 29200 Brest, France. Tel.: +33 398444138; fax: +33 298467910