TY - JOUR T1 - Truncating mutations in exons 20 and 21 of <em>OFD1</em> can cause primary ciliary dyskinesia without associated syndromic symptoms JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2018-105918 SP - jmedgenet-2018-105918 AU - Zuzanna Bukowy-Bieryllo AU - Alicja Rabiasz AU - Maciej Dabrowski AU - Andrzej Pogorzelski AU - Alina Wojda AU - Hanna Dmenska AU - Katarzyna Grzela AU - Jakub Sroczynski AU - Michal Witt AU - Ewa Zietkiewicz Y1 - 2019/07/31 UR - http://jmg.bmj.com/content/early/2019/07/31/jmedgenet-2018-105918.abstract N2 - 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. ER -