PT  - JOURNAL ARTICLE
AU  - M Failly
AU  - L Bartoloni
AU  - A Letourneau
AU  - A Munoz
AU  - E Falconnet
AU  - C Rossier
AU  - M M de Santi
AU  - F Santamaria
AU  - O Sacco
AU  - C D DeLozier-Blanchet
AU  - R Lazor
AU  - J-L Blouin
TI  - Mutations in <em>DNAH5</em> account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia
AID  - 10.1136/jmg.2008.061176
DP  - 2009 Apr 01
TA  - Journal of Medical Genetics
PG  - 281--286
VI  - 46
IP  - 4
4099  - http://jmg.bmj.com/content/46/4/281.short
4100  - http://jmg.bmj.com/content/46/4/281.full
SO  - J Med Genet2009 Apr 01; 46
AB  - Background: Primary ciliary dyskinesia (PCD) is characterised by recurrent infections of the upper respiratory airways (nose, bronchi, and frontal sinuses) and randomisation of left–right body asymmetry. To date, PCD is mainly described with autosomal recessive inheritance and mutations have been found in five genes: the dynein arm protein subunits DNAI1, DNAH5 and DNAH11, the kinase TXNDC3, and the X-linked retinitis pigmentosa GTPase regulator RPGR.Methods: We screened 89 unrelated individuals with PCD for mutations in the coding and splice site regions of the gene DNAH5 by denaturing high performance liquid chromatography (DHPLC) and sequencing. Patients were mainly of European origin and were recruited without any phenotypic preselection.Results: We identified 18 novel (nonsense, splicing, small deletion and missense) and six previously described mutations. Interestingly, these DNAH5 mutations were mainly associated with outer + inner dyneins arm ultrastructural defects (50%).Conclusion: Overall, mutations on both alleles of DNAH5 were identified in 15% of our clinically heterogeneous cohort of patients. Although genetic alterations remain to be identified in most patients, DNAH5 is to date the main PCD gene.