RT Journal Article SR Electronic T1 Delineation of CCDC39/CCDC40 mutation spectrum and associated phenotypes in primary ciliary dyskinesia JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 410 OP 416 DO 10.1136/jmedgenet-2012-100867 VO 49 IS 6 A1 Sylvain Blanchon A1 Marie Legendre A1 Bruno Copin A1 Philippe Duquesnoy A1 Guy Montantin A1 Esther Kott A1 Florence Dastot A1 Ludovic Jeanson A1 Marine Cachanado A1 Alexandra Rousseau A1 Jean François Papon A1 Nicole Beydon A1 Jacques Brouard A1 Bruno Crestani A1 Antoine Deschildre A1 Julie Désir A1 Hélène Dollfus A1 Bruno Leheup A1 Aline Tamalet A1 Caroline Thumerelle A1 Anne-Marie Vojtek A1 Denise Escalier A1 André Coste A1 Jacques de Blic A1 Annick Clément A1 Estelle Escudier A1 Serge Amselem YR 2012 UL http://jmg.bmj.com/content/49/6/410.abstract AB Background CCDC39 and CCDC40 genes have recently been implicated in primary ciliary dyskinesia (PCD) with inner dynein arm (IDA) defects and axonemal disorganisation; their contribution to the disease is, however, unknown. Aiming to delineate the CCDC39/CCDC40 mutation spectrum and associated phenotypes, this study screened a large cohort of patients with IDA defects, in whom clinical and ciliary phenotypes were accurately described.Methods All CCDC39 and CCDC40 exons and intronic boundaries were sequenced in 43 patients from 40 unrelated families. The study recorded and compared clinical features (sex, origin, consanguinity, laterality defects, ages at first symptoms and at phenotype 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 associated with axonemal disorganisation (22 and eight families, respectively). Fourteen of the 28 identified mutations are novel. No mutation was found in the six 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, analysed in 4/7 infertile males, showed evidence of abnormalities similar to the ciliary ones.Conclusions CCDC39 and CCDC40 mutations represent the major cause of PCD with IDA defects and axonemal disorganisation. Patients carrying CCDC39 or CCDC40 mutations are phenotypically indistinguishable. CCDC39 and CCDC40 analyses in selected patients ensure mutations are found with high probability, even if clinical or ciliary phenotypes cannot prioritise one analysis over the other.