Variation in DNAH1 may contribute to primary ciliary dyskinesia.
BACKGROUND
Primary Ciliary Dyskinesia (PCD) is a genetically heterogeneous ciliopathy caused by ultrastructural defects in ciliary or flagellar structure and is characterized by a number of clinical symptoms including recurrent respiratory infections progressing to permanent lung damage and infertility.


METHODS
Here we describe our search to delineate the molecular basis in two affected sisters with clinically diagnosed PCD from a consanguineous Saudi Arabian family, in which all known genes have been excluded. A homozygosity mapping-based approach was utilized that ultimately identified one single affected-shared region of homozygosity using 10 additional unaffected family members. A plausible candidate gene was directly sequenced and analyzed for mutations. A novel homozygous missense aberration (p.Lys1154Gln) was identified in both sisters in the DNAH1 gene that segregated completely with the disease phenotype. Further confirmation of this interesting variant was provided by exome-wide analysis in the proband.


CONCLUSIONS
Molecular variation in DNAH1 may play a role in PCD and its potential contribution should be considered in patients where all known genes are excluded.
Department of Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. fahmad@kfshrc.edu.sa.
Faiqa
F
Imtiaz
Department of Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. Rallam@kfshrc.edu.sa.
Rabab
R
Allam
Department of Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. kramzan@kfshrc.edu.sa.
Khushnooda
K
Ramzan
Department of Medical Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. moeen@kfshrc.edu.sa.
Moeenaldeen
M
Al-Sayed
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004398:Dyneins / Q000737:chemistry / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D006720:Homozygote; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
C000598989:DNAH1 protein, human; D004398:Dyneins