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          Institute: MPI für molekulare Genetik     Collection: Sequencing Group     Display Documents



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ID: 460301.0, MPI für molekulare Genetik / Sequencing Group
Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects.
Authors:Loges, Niki Tomas; Olbrich, Heike; Becker-Heck, Anita; Häffner, Karsten; Heer, Angelina; Reinhard, Christina; Schmidts, Miriam; Kispert, Andreas; Zariwala, Maimoona A.; Leigh, Margaret W.; Knowles, Michael R.; Zentgraf, Hanswalter; Seithe, Horst; Nürnberg, Gudrun; Nürnberg, Peter; Reinhardt, Richard; Omran, Heymut
Language:English
Date of Publication (YYYY-MM-DD):2009-11-25
Title of Journal:American Journal of Human Genetics
Journal Abbrev.:Am J Hum Genet.
Volume:85
Issue / Number:6
Start Page:883
End Page:889
Copyright:2009 The American Society of Human Genetics. All rights reserved.
Review Status:not specified
Audience:Experts Only
Abstract / Description: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.
Comment of the Author/Creator:Corresponding author.
Heymut Omran
External Publication Status:published
Document Type:Article
Communicated by:Richard Reinhardt
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Department of Paediatrics and Adolescent Medicine, University Hospital 79106 Freiburg, Germany;
2.Faculty of Biology, Albert-Ludwigs-University, 79104 Freiburg, Germany;
3.Institut für Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hanover, Germany;
4.Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-3380, USA;
5.Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599-3380, USA;
6.Department of Medicine, University of North Carolina, Chapel Hill, NC 27599-3380, USA;
7.Department of Tumor Virology, German Cancer Research Center, 69120 Heidelberg, Germany;
8.Zentrum für Neugeborene, Kinder und Jugendliche, Klinikum Nürnberg Süd, 90471 Nürnberg, Germany;
9.Cologne Center for Genomics and Institute for Genetics, 50674 Cologne, Germany;
10.Center for Molecular Medicine Cologne, 50931 Cologne, Germany;
11.Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, 50674 Cologne, Germany;
12.Klinik und Poliklinik für Kinder- und Jugendmedizin - Allgemeine Pädiatrie - Universitätsklinikum Münster, Albert-Schweitzer-Strasse 33; 48149 Münster, Germany.
Identifiers:URL:http://www.cell.com/AJHG/retrieve/pii/S00029297090...
DOI:10.1016/j.ajhg.2009.10.018
ISSN:0002-9297
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