Abstract
Primary ciliary dyskinesia (PCD) is a genetic condition of impaired ciliary beating, characterized by chronic infections of the upper and lower airways and progressive lung failure. Defects of the outer dynein arms are the most common cause of PCD. In about half of the affected individuals, PCD occurs with situs inversus (Kartagener syndrome). A minor PCD subgroup including defects of the radial spokes (RS) and central pair (CP) is hallmarked by the absence of laterality defects, subtle beating abnormalities, and unequivocally apparent ultrastructural defects of the ciliary axoneme, making their diagnosis challenging. We identified homozygous loss-of-function mutations in STK36 in one PCD-affected individual with situs solitus. Transmission electron microscopy analysis demonstrates that STK36 is required for cilia orientation in human respiratory epithelial cells, with a probable localization of STK36 between the RS and CP. STK36 screening can now be included for this rare and difficult to diagnose PCD subgroup.
Original language | English |
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Pages (from-to) | 964-969 |
Number of pages | 6 |
Journal | Human Mutation |
Volume | 38 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2017 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 Wiley Periodicals, Inc.
Funding
The authors thank the individuals affected by PCD and their families for their participation and acknowledge the German patient support group “Kartagener Syndrome und Primaere Ciliaere Dyskinesie e.V.” We thank Anja Kolb-Kokocinski, Yasin Memari, and Richard Durbin (Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom) for their help in processing and analyzing the whole-exome sequencing data. We also thank M. Herting, A. Robbers, L. Overkamp, and K. Wohlgemuth for their technical assistance. We thank R. Hjeij, I. Hoeben, T. Kaiser, T. Menchen, and C. Werner for helpful discussions. The authors have no conflict of interest to declare.
Funders | Funder number |
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Kartagener Syndrome und Primaere Ciliaere Dyskinesie | |
Wellcome Trust Sanger Institute |
Keywords
- STK36
- central pair
- motile cilia
- primary ciliary dyskinesia
- radial spokes