2. Academic Validation
  3. Variation in DNAH1 may contribute to primary ciliary dyskinesia

Variation in DNAH1 may contribute to primary ciliary dyskinesia

  • BMC Med Genet. 2015 Mar 17;16:14. doi: 10.1186/s12881-015-0162-5.
Faiqa Imtiaz 1,  Rabab Allam 2,  Khushnooda Ramzan 3,  Moeenaldeen Al-Sayed 4
Affiliations

Affiliations

  • 1 Department of Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. fahmad@kfshrc.edu.sa.
  • 2 Department of Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. Rallam@kfshrc.edu.sa.
  • 3 Department of Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. kramzan@kfshrc.edu.sa.
  • 4 Department of Medical Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia. moeen@kfshrc.edu.sa.
PMID: 25927852 DOI: 10.1186/s12881-015-0162-5
Abstract

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.

Case presentation: 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.

Conclusion: 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.

Figures