• PMID: 31366608
• Gene Name: OFD1
• Condition: Primary ciliary dyskinesia, Male infertility
• Association: Associated
• Mutation: Truncation of exons 16-22
• Population size: 120
• Population details: 120 Polish PCD patients
• Sex: Male
• Infertility type: Male infertility

Truncating mutations in exons 20 and 21 of OFD1 can cause primary ciliary dyskinesia without associated syndromic symptoms

Bukowy-Bieryllo Z, Rabiasz A, Dabrowski M, Pogorzelski A, Wojda A, Dmenska H, Grzela K, Sroczynski J, Witt M, Zietkiewicz E.

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. CI - © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Bukowy-Bieryllo, Zuzanna AU - Bukowy-Bieryllo Z AUID- ORCID: 0000-0002-6945-1059 AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland zuzanna.bukowy-bieryllo@igcz.poznan.pl. FAU - Rabiasz, Alicja AU - Rabiasz A AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Dabrowski, Maciej AU - Dabrowski M AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Pogorzelski, Andrzej AU - Pogorzelski A AD - Rabka Branch, Institute of Tuberculosis and Lung Diseases, Rabka-Zdroj, Poland. FAU - Wojda, Alina AU - Wojda A AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Dmenska, Hanna AU - Dmenska H AD - Department of Lung Physiology, Children's Memorial Health Institute, Warsaw, Poland. FAU - Grzela, Katarzyna AU - Grzela K AD - Departments of Pulmonology and Allergy, Warsaw Medical University, Warsaw, Poland. FAU - Sroczynski, Jakub AU - Sroczynski J AD - Department of Paediatric Otolaryngology, Poznan University of Medical Sciences, Poznan, Wielkopolskie, Poland. FAU - Witt, Michal AU - Witt M AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.