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Original research
Truncating mutations in exons 20 and 21 of OFD1 can cause primary ciliary dyskinesia without associated syndromic symptoms
  1. Zuzanna Bukowy-Bieryllo1,
  2. Alicja Rabiasz1,
  3. Maciej Dabrowski1,
  4. Andrzej Pogorzelski2,
  5. Alina Wojda1,
  6. Hanna Dmenska3,
  7. Katarzyna Grzela4,
  8. Jakub Sroczynski5,
  9. Michal Witt1,
  10. Ewa Zietkiewicz1
  1. 1 Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland
  2. 2 Rabka Branch, Institute of Tuberculosis and Lung Diseases, Rabka-Zdroj, Poland
  3. 3 Department of Lung Physiology, Children’s Memorial Health Institute, Warsaw, Poland
  4. 4 Departments of Pulmonology and Allergy, Warsaw Medical University, Warsaw, Poland
  5. 5 Department of Paediatric Otolaryngology, Poznan University of Medical Sciences, Poznan, Wielkopolskie, Poland
  1. Correspondence to Dr Zuzanna Bukowy-Bieryllo, Institute of Human Genetics, Polish Academy of Sciences, Poznan 60-479, Poland; zuzanna.bukowy-bieryllo{at}


Background Primary ciliary dyskinesia (PCD) is a motile ciliopathy, whose symptoms include airway infections, male infertility and situs inversus. Apart from the typical forms of PCD, rare syndromic PCD forms exist. Mutations of the X-linked OFD1 gene cause several syndromic ciliopathies, including oral-facial-digital syndrome type 1, Joubert syndrome type 10 (JBTS10), and Simpson-Golabi-Behmel syndrome type 2, the latter causing the X-linked syndromic form of PCD. Neurological and skeletal symptoms are characteristic for these syndromes, with their severity depending on the location of the mutation within the gene.

Objectives To elucidate the role of motile cilia defects in the respiratory phenotype of PCD patients with C-terminal OFD1 mutations.

Methods Whole-exome sequencing in a group of 120 Polish PCD patients, mutation screening of the OFD1 coding sequence, analysis of motile cilia, and magnetic resonance brain imaging.

Results Four novel hemizygous OFD1 mutations, in exons 20 and 21, were found in men with a typical PCD presentation but without severe neurological, skeletal or renal symptoms characteristic for other OFD1-related syndromes. Magnetic resonance brain imaging in two patients did not show a molar tooth sign typical for JBTS10. Cilia in the respiratory epithelium were sparse, unusually long and displayed a defective motility pattern.

Conclusion Consistent with the literature, truncations of the C-terminal part of OFD1 (exons 16–22) almost invariably cause a respiratory phenotype (due to motile cilia defects) while their impact on the primary cilia function is limited. We suggest that exons 20–21 should be included in the panel for regular mutation screening in PCD.

  • oral-facial digital syndrome type 1
  • primary ciliary dyskinesia
  • syndromic PCD
  • Joubert syndrome type 10
  • Simpson-Golabi-Behmel syndrome type 2
  • ciliopathy
  • motile cilia biogenesis

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  • AR and MD contributed equally.

  • Contributors EZ, ZBB and AR participated in the design of the study. ZBB, AR, AW, MD, AP, KG, HG, JS collected and/or generated the data. ZBB, AR, MD, EZ, AP, HD, KG analysed and/or interpreted the data. ZBB, EZ, AR, MW drafted the manuscript. All authors corrected the manuscript.

  • Funding The authors of this manuscript have been supported by the funding from the Polish National Science Center, Poland, granted based on decision number DEC 2014/13/B/NZ2/03858 (EZ) and DEC- 2013/09/D/NZ4/01692 (ZBB). The funding bodies did not have any influence on the design of the study, or its results or the manuscript preparation. Authors of this manuscript are participants in BEAT-PCD project (COST Action BM 1407).

  • Competing interests ZBB, AR, MD, AW, MW and EZ report grants from National Science Center, Poland, during the conduct of the study (funding granted to EZ and ZBB). ZBB reports also personal fees from National Science Centre, Poland during the conduct of the study. ZBB and AW report personal fees from National Science Centre, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.