Loss-of-function GAS8 mutations cause primary ciliary dyskinesia and disrupt the nexin-dynein regulatory complex

Item Type:	Article
Title:	Loss-of-function GAS8 mutations cause primary ciliary dyskinesia and disrupt the nexin-dynein regulatory complex
Creators Name:	Olbrich, H. and Cremers, C. and Loges, N.T. and Werner, C. and Nielsen, K.G. and Marthin, J.K. and Philipsen, M. and Wallmeier, J. and Pennekamp, P. and Menchen, T. and Edelbusch, C. and Dougherty, G.W. and Schwartz, O. and Thiele, H. and Altmüller, J. and Rommelmann, F. and Omran, H.
Abstract:	Multiciliated epithelial cells protect the upper and lower airways from chronic bacterial infections by moving mucus and debris outward. Congenital disorders of ciliary beating, referred to as primary ciliary dyskinesia (PCD), are characterized by deficient mucociliary clearance and severe, recurrent respiratory infections. Numerous genetic defects, most of which can be detected by transmission electron microscopy (TEM), are so far known to cause different abnormalities of the ciliary axoneme. However, some defects are not regularly discernable by TEM because the ciliary architecture of the axoneme remains preserved. This applies in particular to isolated defects of the nexin links, also known as the nexin-dynein regulatory complex (N-DRC), connecting the peripheral outer microtubular doublets. Immunofluorescence analyses of respiratory cells from PCD-affected individuals detected a N-DRC defect. Genome-wide exome sequence analyses identified recessive loss-of-function mutations in GAS8 encoding DRC4 in three independent PCD-affected families.
Keywords:	Cilia, Cytoskeletal Proteins, Dyneins, Exome, Fluorescence Microscopy, Intracellular Signaling Peptides and Proteins, Kartagener Syndrome, Knockout Mice, Membrane Proteins, Multiprotein Complexes, Mutation, Nasal Mucosa, Neoplasm Proteins, Nitric Oxide, Pedigree, Phenotype, Prognosis, Protease Nexins, Respiratory System, Signal Transducing Adaptor Proteins, Transmission Electron Microscopy, Western Blotting, Young Adult, Animals, Mice
Source:	American Journal of Human Genetics
ISSN:	0002-9297
Publisher:	Elsevier / Cell Press
Volume:	97
Number:	4
Page Range:	546-54
Date:	1 October 2015
Additional Information:	Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Official Publication:	https://doi.org/10.1016/j.ajhg.2015.08.012
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

Repository Staff Only: item control page