RT Journal Article SR Electronic T1 Mutations of DNAH11 in patients with primary ciliary dyskinesia with normal ciliary ultrastructure JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP 433 OP 441 DO 10.1136/thoraxjnl-2011-200301 VO 67 IS 5 A1 Michael R Knowles A1 Margaret W Leigh A1 Johnny L Carson A1 Stephanie D Davis A1 Sharon D Dell A1 Thomas W Ferkol A1 Kenneth N Olivier A1 Scott D Sagel A1 Margaret Rosenfeld A1 Kimberlie A Burns A1 Susan L Minnix A1 Michael C Armstrong A1 Adriana Lori A1 Milan J Hazucha A1 Niki T Loges A1 Heike Olbrich A1 Anita Becker-Heck A1 Miriam Schmidts A1 Claudius Werner A1 Heymut Omran A1 Maimoona A Zariwala A1 for the Genetic Disorders of Mucociliary Clearance Consortium YR 2012 UL http://thorax.bmj.com/content/67/5/433.abstract AB Rationale Primary ciliary dyskinesia (PCD) is an autosomal recessive, genetically heterogeneous disorder characterised by oto-sino-pulmonary disease and situs abnormalities (Kartagener syndrome) due to abnormal structure and/or function of cilia. Most patients currently recognised to have PCD have ultrastructural defects of cilia; however, some patients have clinical manifestations of PCD and low levels of nasal nitric oxide, but normal ultrastructure, including a few patients with biallelic mutations in dynein axonemal heavy chain 11 (DNAH11).Objectives To test further for mutant DNAH11 as a cause of PCD, DNAH11 was sequenced in patients with a PCD clinical phenotype, but no known genetic aetiology.Methods 82 exons and intron/exon junctions in DNAH11 were sequenced in 163 unrelated patients with a clinical phenotype of PCD, including those with normal ciliary ultrastructure (n=58), defects in outer and/or inner dynein arms (n=76), radial spoke/central pair defects (n=6), and 23 without definitive ultrastructural results, but who had situs inversus (n=17), or bronchiectasis and/or low nasal nitric oxide (n=6). Additionally, DNAH11 was sequenced in 13 subjects with isolated situs abnormalities to see if mutant DNAH11 could cause situs defects without respiratory disease.Results Of the 58 unrelated patients with PCD with normal ultrastructure, 13 (22%) had two (biallelic) mutations in DNAH11; and two patients without ultrastructural analysis had biallelic mutations. All mutations were novel and private. None of the patients with dynein arm or radial spoke/central pair defects, or isolated situs abnormalities, had mutations in DNAH11. Of the 35 identified mutant alleles, 24 (69%) were nonsense, insertion/deletion or loss-of-function splice-site mutations.Conclusions Mutations in DNAH11 are a common cause of PCD in patients without ciliary ultrastructural defects; thus, genetic analysis can be used to ascertain the diagnosis of PCD in this challenging group of patients.