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Extended report
Mutations of the cystic fibrosis gene in patients with bronchiectasis associated with rheumatoid arthritis
  1. Xavier Puéchal1,2,
  2. Thierry Bienvenu3,
  3. Emmanuelle Génin4,5,
  4. Jean-Marie Berthelot6,
  5. Jean Sibilia7,
  6. Philippe Gaudin8,
  7. Christian Marcelli9,
  8. Sandra Lasbleiz10,
  9. Laëtitia Michou10,
  10. François Cornélis10,
  11. André Kahan2,
  12. Daniel J Dusser11
  1. 1Center for Rare Systemic Auto-immune Diseases, Department of Rheumatology, Centre Hospitalier du Mans, Le Mans, France
  2. 2Department of Rheumatology A, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
  3. 3Biochemistry and Molecular Biology Laboratory, Hôpital Cochin, AP-HP, Paris, France
  4. 4INSERM UMR-S946, Paris, France
  5. 5Université Paris Diderot, Paris, France
  6. 6Department of Rheumatology, Hôtel Dieu, Nantes, France
  7. 7Department of Rheumatology, Hôpital Hautepierre, Strasbourg, France
  8. 8Department of Rheumatology, Hôpital Sud A Michallon, Grenoble, France
  9. 9Department of Rheumatology, Hôpital de la Côte de Nacre, Caen, France
  10. 10GenHotel-EA3886, Universités Evry-Paris VII, Evry-Genopole, Evry, France
  11. 11Department of Respiratory Diseases, Université Paris Descartes, Hôpital Cochin, AP-HP, Paris, France
  1. Correspondence to Dr Xavier Puéchal, Center for Rare Systemic Auto-immune Diseases, Department of Rheumatology, Centre Hospitalier du Mans, 194 avenue Rubillard, 72000 Le Mans, France; xpuechal{at}


Objectives In cystic fibrosis, mutations of the CFTR gene lead to diffuse bronchiectasis (DB). DB is also associated with other diseases including rheumatoid arthritis (RA) in which the role of genetic factors in the predisposition to DB remains unclear.

Methods A family-based association study was carried out to determine whether the frequency of CFTR mutations was higher in patients with RA-associated DB and to determine whether a causal relationship could be established between the variant and the disease by evaluating its cosegregation with DB within families. Families of probands with RA-DB were included if one first-degree relative had RA and/or DB. The controls comprised healthy subjects requesting genetic counselling because their partner had cystic fibrosis.

Results The frequency of CFTR mutations was higher in family members with RA-DB or DB only than in unaffected relatives (p<0.005 for each comparison) and in unrelated healthy controls (p<0.001 for each comparison) but not in family members with RA only. CFTR mutations were more frequent in family members with RA-DB than in those with RA only (OR 5.30, 95% CI 2.48 to 11.33; p<5×10−5). They cosegregated with RA-DB in the families (sib-TDT=10.82, p=0.005).

Conclusions RA-DB should be added to the list of phenotypes in which CFTR mutations are pathogenic. CFTR mutation is the first genetic defect linked to an extra-articular feature of RA to be described. CFTR mutations in patients with RA appear to be an important marker of the risk of associated DB, which has been linked to a less favourable prognosis.

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  • Funding This work was supported by grants from the Assistance Publique-Hôpitaux de Paris (Contrat de Recherche et d'Innovation Clinique CRC98046) (to XP) and the Société Française de Rhumatologie (to XP).

  • Competing interests None.

  • Ethics approval The study protocol was reviewed and approved by the institutional review board for clinical research of Assistance Publique-Hôpitaux de Paris and the ethics committee of the Medical Faculty of René Descartes University, Paris.

  • Provenance and peer review Not commissioned; externally peer reviewed.