Volume 1 Supplement 1

Proceedings of the First International Cilia in Development and Disease Scientific Conference (2012)

Open Access

Delineation of CCDC39/CCDC40 mutation spectrum and associated phenotypes in primary ciliary dyskinesia

  • M Legendre1Email author,
  • S Blanchon1, 2,
  • B Copin1,
  • P Duquesnoy1,
  • G Montantin1,
  • E Kott1,
  • F Dastot1,
  • L Jeanson1,
  • M Cachanado3,
  • A Rousseau3,
  • JF Papon4,
  • A Tamalet2,
  • AM Vojtek5,
  • D Escalier1,
  • A Coste4,
  • J de Blic6,
  • A Clément2,
  • E Escudier1 and
  • S Amselem1
Cilia20121(Suppl 1):P91

DOI: 10.1186/2046-2530-1-S1-P91

Published: 16 November 2012


CCDC39 and CCDC40 genes have recently been implicated in primary ciliary dyskinesia (PCD) with inner dynein arms (IDA) defects and axonemal disorganization; their contribution to the disease is, however, unknown. With the aim to delineate CCDC39/CCDC40 mutation spectrum and associated phenotypes, we screened a large cohort of patients with IDA defects, and accurately described their clinical and ciliary phenotypes.


All CCDC39 and CCDC40 exons and intronic boundaries were sequenced in 43 patients from 40 unrelated families. We recorded and compared clinical features (sex, origin, consanguinity, laterality defects, ages at first symptoms and evaluation, neonatal respiratory distress, airway infections, nasal polyposis, otitis media, bronchiectasis, infertility), ciliary beat frequency and quantitative ultrastructural analyses of cilia and sperm flagella.


Biallelic CCDC39 or CCDC40 mutations were identified in 30/34 (88.2%) unrelated families with IDA defects and axonemal disorganization (22 and 8 families, respectively). Fourteen of the 28 identified mutations are novel. No mutation was found in the 6 families with isolated IDA defects. Patients with identified mutations shared a similar phenotype, in terms of both clinical features and ciliary structure and function. The sperm flagellar ultrastructure, analyzed in 4/7 infertile males, evidenced abnormalities similar to the ciliary ones.


CCDC39 and CCDC40 mutations represent the major cause of PCD with IDA defects and axonemal disorganization. Patients carrying CCDC39 or CCDC40 mutations are phenotypically indistinguishable. CCDC39 and CCDC40 analyses in selected patients ensure to find mutations with high probability, even if clinical or ciliary phenotypes cannot prioritize one analysis over the other.

Authors’ Affiliations

INSERM, UMR_S933, UPMC Univ Paris 06; and AP-HP, Service de Génétique et d’Embryologie Médicales, Hôpital Armand-Trousseau
Unité de Pneumologie Pédiatrique, Centre National de Référence des Maladies Respiratoires Rares, AP-HP, Hôpital Armand-Trousseau
Unité de Recherche Clinique; and UPMC Univ Paris 06, Unité Fonctionnelle de Pharmacologie, AP-HP, Hôpital Saint-Antoine
Service d’ORL et de Chirurgie Cervico-Faciale, AP-HP, Hôpital Inter-Communal et Groupe Hospitalier Henri Mondor-Albert Chenevier
Hôpital Inter-Communal, Service d’Anatomo-Pathologie
Service de Pneumologie et Allergologie Pédiatriques, AP-HP, Groupe Hospitalier Necker-Enfants Malades


© Legendre et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.