Journal article
Primary Ciliary Dyskinesia Caused by Homozygous Mutation in DNAL1, Encoding Dynein Light Chain 1
American journal of human genetics, Vol.88(5), pp.599-607
05/13/2011
DOI: 10.1016/j.ajhg.2011.03.018
PMCID: PMC3146731
PMID: 21496787
Abstract
In primary ciliary dyskinesia (PCD), genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility. 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. Although it has long been suspected that mutations in
DNAL1
encoding the ODA light chain1 might cause PCD such mutations were not found. We demonstrate here that a homozygous point mutation in this gene is associated with PCD with absent or markedly shortened ODA. The mutation (NM_031427.3: c.449A>G; p.Asn150Ser) changes the Asn at position150, which is critical for the proper tight turn between the β strand and the α helix of the leucine-rich repeat in the hydrophobic face that connects to the dynein heavy chain. The mutation reduces the stability of the axonemal dynein light chain 1 and damages its interactions with dynein heavy chain and with tubulin. This study adds another important component to understanding the types of mutations that cause PCD and provides clinical information regarding a specific mutation in a gene not yet known to be associated with PCD.
Details
- Title: Subtitle
- Primary Ciliary Dyskinesia Caused by Homozygous Mutation in DNAL1, Encoding Dynein Light Chain 1
- Creators
- Masha Mazor - Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, IsraelSoliman Alkrinawi - Division of Pediatrics, Soroka University Medical Center, Beer Sheva 84101, IsraelVered Chalifa-Caspi - National Institute of Biotechnology in the Negev, Ben Gurion University of the Negev, Beer Sheva 84105, IsraelEsther Manor - Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, IsraelVal C Sheffield - Department of Pediatrics, Division of Medical Genetics, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USAMicha Aviram - Division of Pediatrics, Soroka University Medical Center, Beer Sheva 84101, IsraelRuti Parvari - Department of Virology and Developmental Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.88(5), pp.599-607
- Publisher
- Elsevier
- DOI
- 10.1016/j.ajhg.2011.03.018
- PMID
- 21496787
- PMCID
- PMC3146731
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Language
- English
- Date published
- 05/13/2011
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984065393502771
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