Heterozygous cis HYDIN mutations cause primary ciliary dyskinesia

Area of Science:

• Genetics
• Cell Biology
• Respiratory Medicine

Background:

• The HYDIN gene is crucial for motile cilia central pair (CP) structure.
• Mutations in HYDIN cause primary ciliary dyskinesia (PCD), a disorder of defective mucociliary clearance.
• PCD leads to chronic lung disease due to impaired mucus removal.

Purpose of the Study:

• To diagnose and characterize a novel genetic cause of primary ciliary dyskinesia (PCD) in two siblings.
• To investigate the role of HYDIN mutations in ciliary dysfunction.
• To explore disease manifestation without typical biallelic mutations.

Main Methods:

• Nasal airway epithelial cells (NAECs) were cultured from affected siblings.
• Cilia structure and function were analyzed using high-speed video microscopy (HSVM).
• Immunofluorescence and transmission electron microscopy confirmed defects in cilia axoneme components.

Main Results:

• Cultured NAECs exhibited abnormal cilia beating patterns.
• Loss of HYDIN and SPEF2 proteins from the cilia axoneme was observed.
• Two novel, cis-acting HYDIN mutations were identified in both siblings.

Conclusions:

• This case report describes the diagnosis of PCD in siblings with previously unreported HYDIN mutations.
• The findings suggest that disease can occur without biallelic mutations in ciliary genes.
• This expands the understanding of genetic mechanisms underlying primary ciliary dyskinesia.