title: DNAI1 mutations explain only 2% of primary ciliary dykinesia.
abstract: BACKGROUND
  Primary ciliary dyskinesia (PCD) is a rare recessive hereditary disorder characterized by dysmotility to immotility of ciliated and flagellated structures. Its main symptoms are respiratory, caused by defective ciliary beating in the epithelium of the upper airways (nose, bronchi and paranasal sinuses). Impairing the drainage of inhaled microorganisms and particles leads to recurrent infections and pulmonary complications. To date, 5 genes encoding 3 dynein protein arm subunits (DNAI1, DNAH5 and DNAH11), the kinase TXNDC3 and the X-linked RPGR have been found to be mutated in PCD.
  
  
  OBJECTIVE
  We proposed to determine the impact of the DNAI1 gene on a cohort of unrelated PCD patients (n = 104) recruited without any phenotypic preselection.
  
  
  METHODS
  We used denaturing high-performance liquid chromatography and sequencing to screen for mutations in the coding and splicing site sequences of the gene DNAI1.
  
  
  RESULTS
  Three mutations were identified: a novel missense variant (p.Glu174Lys) was found in 1 patient and 2 previously reported variants were identified (p.Trp568Ser in 1 patient and IVS1+2_3insT in 3 patients). Overall, mutations on both alleles of gene DNAI1 were identified in only 2% of our clinically heterogeneous cohort of patients.
  
  
  CONCLUSIONS
  We conclude that DNAI1 gene mutation is not a common cause of PCD, and that major or several additional disease gene(s) still remain to be identified before a sensitive molecular diagnostic test can be developed for PCD.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Mike
authors.initials: M
authors.lastname: Failly
authors.forename: Alexandra
authors.initials: A
authors.lastname: Saitta
authors.forename: Analia
authors.initials: A
authors.lastname: Muñoz
authors.forename: Emilie
authors.initials: E
authors.lastname: Falconnet
authors.forename: Colette
authors.initials: C
authors.lastname: Rossier
authors.forename: Francesca
authors.initials: F
authors.lastname: Santamaria
authors.forename: Maria Margherita
authors.initials: MM
authors.lastname: de Santi
authors.forename: Romain
authors.initials: R
authors.lastname: Lazor
authors.forename: Celia D
authors.initials: CD
authors.lastname: DeLozier-Blanchet
authors.forename: Lucia
authors.initials: L
authors.lastname: Bartoloni
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blouin
mesh_terms: D000595:Amino Acid Sequence; D056444:Axonemal Dyneins; D004252:DNA Mutational Analysis; D004398:Dyneins / Q000235:genetics*; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data
chemical_list: C425071:DNAI1 protein, human; D056444:Axonemal Dyneins; D004398:Dyneins