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Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry
Heike Olbrich1, Karsten Häffner, Andreas Kispert
1Department of Pediatrics and Adolescent Medicine, Albert Ludwigs University, 79106 Freiburg, Germany.
Abstract:
Primary ciliary dyskinesia (PCD, MIM 242650) is characterized by recurrent infections of the respiratory tract due to reduced mucociliary clearance and by sperm immobility. Half of the affected offspring have situs inversus (reversed organs), which results from randomization of left-right (LR) asymmetry. We previously localized to chromosome 5p a PCD locus containing DNAH5, which encodes a protein highly similar to the Chlamydomonas gamma-dynein heavy chain. Here we characterize the full-length 14-kb transcript of DNAH5. Sequence analysis in individuals with PCD with randomization of LR asymmetry identified mutations resulting in non-functional DNAH5 proteins.
Insights
Primary ciliary dyskinesia (PCD) involves respiratory infections and immobility due to impaired mucociliary clearance. Mutations in the DNAH5 gene cause non-functional proteins, leading to PCD and randomization of left-right body asymmetry.
Area of Science:
- Genetics
- Cell Biology
- Developmental Biology
Background:
- Primary ciliary dyskinesia (PCD) is a genetic disorder affecting mucociliary clearance, leading to recurrent respiratory infections and male infertility.
- Approximately 50% of PCD patients exhibit situs inversus, indicating a defect in left-right body asymmetry determination.
Purpose of the Study:
- To characterize the full-length transcript of the DNAH5 gene.
- To investigate the role of DNAH5 mutations in PCD, particularly in cases with randomization of left-right asymmetry.
Main Methods:
- Full-length 14-kb transcript of DNAH5 was characterized.
- Sequence analysis was performed on individuals with PCD and situs inversus.
Main Results:
- Mutations in the DNAH5 gene were identified in individuals with PCD and randomization of left-right asymmetry.
- These mutations result in non-functional DNAH5 proteins, implicating DNAH5 in both ciliary function and embryonic asymmetry.
Conclusions:
- DNAH5 is a critical gene for normal ciliary function and the establishment of left-right body asymmetry.
- Mutations in DNAH5 are a cause of primary ciliary dyskinesia and associated randomization of asymmetry.