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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1396797

Novel pathogenic variants in DNAH5 associated with Clinical and Genetic Spectrum of Primary Ciliary Dyskinesia in an Arab population

Provisionally accepted
Dalal Al-Mutairi Dalal Al-Mutairi 1*Basel Alsabah Basel Alsabah 2Petra Pennekamp Petra Pennekamp 3Heymut Omran Heymut Omran 3
  • 1 Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, Safat, 13110, Kuwait, Kuwait, Kuwait
  • 2 Other, Kuwait City, Kuwait
  • 3 Department of General Pediatrics, University Hospital Münster, Münster, Germany

The final, formatted version of the article will be published soon.

    Introduction: Primary ciliary dyskinesia (PCD) is caused by dysfunction of motile cilia resulting in insufficient mucociliary clearance of the lungs. The aim of this study is to map novel PCD variants and determine their pathogenicity in PCD patients in Kuwait. Methods: Here we present five PCD individuals belonging to a cohort of 105 PCD individuals recruited from different hospitals in Kuwait. Genomic DNA from the family members was analysed to screen for pathogenic PCDvariants. Transmission electron microscopy (TEM) and immunofluorescence (IF) analyses were performed on nasal biopsies to detect specific structural abnormalities within the ciliated cells. Results: Genetic screening and functional analyses confirmed that the five PCD individuals carry novel pathogenic variants in DNAH5 that cause PCD in three Arabic families; One multiplex family with two affected individuals has two novel homozygous missense variants in DNAH5 causing PCD with situs inversus. Another multiplex family with two affected individuals has two newly identified compound heterozygous variants in DNAH5 causing PCD with situs solitus. In addition, novel heterozygous variants were identified in a child with PCD and situs solitus from a singleton family with unrelated parents. TEM analysis demonstrated a lack of outer dynein arms (ODA) in all analysed samples. IF analysis confirmed absence of dynein arm component DNAH5 from the ciliary axoneme. Conclusions: Newly identified pathogenic variants in DNAH5 are associated with PCD with variable pulmonary clinical manifestations in Arabic families.

    Keywords: primary ciliary dyskinesia, Pulmonary diseases, Genetics of ciliopathy, DNAH5 gene, laterality defects

    Received: 06 Mar 2024; Accepted: 20 May 2024.

    Copyright: © 2024 Al-Mutairi, Alsabah, Pennekamp and Omran. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dalal Al-Mutairi, Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, Safat, 13110, Kuwait, Kuwait, Kuwait

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.