HYDIN variants cause primary ciliary dyskinesia in the Finnish population.

Autor: Burgoyne T; Institute of Ophthalmology, University College London, London, UK.; PCD Diagnostic Team and Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK., Fassad MR; Great Ormond Street Institute of Child Health, University College London, London, UK.; Human Genetics Department, Medical Research Institute, Alexandria University, Alexandria, Egypt., Schultz R; Allergy Centre, Tampere University Hospital, Tampere, Finland., Elenius V; Department of Pediatrics, Turku University Hospital, University of Turku, Turku, Finland., Lim JSY; Great Ormond Street Institute of Child Health, University College London, London, UK., Freke G; Great Ormond Street Institute of Child Health, University College London, London, UK., Rai R; PCD Diagnostic Team and Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK., Mohammed MA; Great Ormond Street Institute of Child Health, University College London, London, UK.; Biochemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt., Mitchison HM; Great Ormond Street Institute of Child Health, University College London, London, UK., Sironen AI; Great Ormond Street Institute of Child Health, University College London, London, UK.; Natural Resources Institute Finland (Luke), Jokioinen, Finland.
Jazyk: angličtina
Zdroj: Pediatric pulmonology [Pediatr Pulmonol] 2024 Sep 18. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1002/ppul.27267
Abstrakt: Introduction: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell. Thus far, disease causing variants in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics and management.
Methods: Whole exome sequencing was used to identify disease causing variants in Finnish PCD cohort. The effect of the identified HYDIN variants on cilia structure and function was confirmed by high-speed video analysis, immunofluorescence and electron tomography.
Results: In this study, we identified three Finnish PCD patients carrying homozygous loss-of-function variants and one patient with compound heterozygous variants within HYDIN. The functional studies showed defects in the axonemal central pair complex. All patients had clinical PCD symptoms including chronic wet cough and recurrent airway infections, associated with mostly static airway cilia.
Conclusion: Our results are consistent with the previously identified important role of HYDIN in the axonemal central pair complex and improve specific diagnostics of PCD in different national populations.
(© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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