2. Academic Validation
  3. Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects

Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects

  • Am J Hum Genet. 2009 Dec;85(6):883-9. doi: 10.1016/j.ajhg.2009.10.018.
Niki Tomas Loges 1,  Heike Olbrich,  Anita Becker-Heck,  Karsten Häffner,  Angelina Heer,  Christina Reinhard,  Miriam Schmidts,  Andreas Kispert,  Maimoona A Zariwala,  Margaret W Leigh,  Michael R Knowles,  Hanswalter Zentgraf,  Horst Seithe,  Gudrun Nürnberg,  Peter Nürnberg,  Richard Reinhardt,  Heymut Omran
Affiliations

Affiliation

  • 1 Department of Paediatrics and Adolescent Medicine, University Hospital 79106 Freiburg, Germany.
PMID: 19944400 DOI: 10.1016/j.ajhg.2009.10.018
Abstract

Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility in primary ciliary dyskinesia (PCD). The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein complexes responsible for cilia-beat generation and regulation, respectively. Here, we demonstrate that large genomic deletions, as well as point mutations involving LRRC50, are responsible for a distinct PCD variant that is characterized by a combined defect involving assembly of the ODAs and IDAs. Functional analyses showed that LRRC50 deficiency disrupts assembly of distally and proximally DNAH5- and DNAI2-containing ODA complexes, as well as DNALI1-containing IDA complexes, resulting in immotile cilia. On the basis of these findings, we assume that LRRC50 plays a role in assembly of distinct dynein-arm complexes.

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