Truncating mutations in exons 20 and 21 of can cause primary ciliary dyskinesia without associated syndromic symptoms.

Background: Primary ciliary dyskinesia (PCD) is a motile ciliopathy, whose symptoms include airway infections, male infertility and . Apart from the typical forms of PCD, rare syndromic PCD forms exist. Mutations of the X-linked 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 coding sequence, analysis of motile cilia, and magnetic resonance brain imaging.

Results: Four novel hemizygous 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 -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 (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.