2046-2530-1-S1-P91 2046-2530 Poster presentation <p>Delineation of <it>CCDC39/CCDC40</it> mutation spectrum and associated phenotypes in primary ciliary dyskinesia</p> LegendreMmarie.legendre@trs.aphp.fr BlanchonS CopinB DuquesnoyP MontantinG KottE DastotF JeansonL CachanadoM RousseauA PaponJF TamaletA VojtekAM EscalierD CosteA de BlicJ ClémentA EscudierE AmselemS

INSERM, UMR_S933, UPMC Univ Paris 06; and AP-HP, Hôpital Armand-Trousseau, Service de Génétique et d’Embryologie Médicales, F-75012, Paris, France

AP-HP, Hôpital Armand-Trousseau, Unité de Pneumologie Pédiatrique, Centre National de Référence des Maladies Respiratoires Rares, F-75012, Paris, France

AP-HP, Hôpital Saint-Antoine, Unité de Recherche Clinique; and UPMC Univ Paris 06, Unité Fonctionnelle de Pharmacologie, F-75012, Paris, France

AP-HP, Hôpital Inter-Communal et Groupe Hospitalier Henri Mondor-Albert Chenevier, Service d’ORL et de Chirurgie Cervico-Faciale, F-94000, Créteil, France

Hôpital Inter-Communal, Service d’Anatomo-Pathologie, F-94000, Créteil, France

AP-HP, Groupe Hospitalier Necker-Enfants Malades, Service de Pneumologie et Allergologie Pédiatriques, F-75015, Paris, France

 Cilia <p>Proceedings of the First International Cilia in Development and Disease Scientific Conference (2012) </p>Phil L Beales and Hannah M MitchisonThis supplement has not been supported by sponsorship or other external funding.Meeting abstracts<p>First International Cilia in Development and Disease Scientific Conference (2012)</p>London, UK16-18 May 2012http://www.ciliopathyalliance.org/2046-2530 2012 1 Suppl 1 P91 http://www.ciliajournal.com/content/1/S1/P91 10.1186/2046-2530-1-S1-P91 16112012 2012Legendre et al; licensee 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.

Background

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.

Methods

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.

Results

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.

Conclusions

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.