DNAI1 mutations explain only 2% of primary ciliary dykinesia.
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.
Failly
Mike
M
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
Saitta
Alexandra
A
Muñoz
Analia
A
Falconnet
Emilie
E
Rossier
Colette
C
Santamaria
Francesca
F
de Santi
Maria Margherita
MM
Lazor
Romain
R
DeLozier-Blanchet
Celia D
CD
Bartoloni
Lucia
L
Blouin
Jean-Louis
JL
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
C425071:DNAI1 protein, human; D056444:Axonemal Dyneins; D004398:Dyneins