To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Hereditary myopathy with … - University of Gothenburg, Sweden Till startsida
To content Read more about how we use cookies on

Hereditary myopathy with early respiratory failure is associated with misfolding of the titin fibronectin III 119 subdomain

Journal article
Authors Carola Hedberg
Alejandro Gomez Toledo
Claes M Gustafsson
Göran Larson
Anders Oldfors
Bertil Macao
Published in Neuromuscular Disorders
Volume 24
Issue 5
Pages 373-379
ISSN 0960-8966
Publication year 2014
Published at Institute of Biomedicine, Department of Pathology
Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 373-379
Language en
Keywords Myopathy; HMERF; Titin; Protein aggregates; Mutation
Subject categories Neurosciences, Neurology


Hereditary myopathy with early respiratory failure is a rare disease with muscle weakness and respiratory failure as early symptoms. Muscle pathology is characterized by the presence of multiple cytoplasmic bodies and other protein aggregates in muscle fibers. The disease is associated with mutations in the titin gene (TTN). All patients harbor mutations located in exon 343 in the TTN gene that codes for the fibronectin III domain 119 (FN3 119) in the 10th motif of the 11-element motif A-band super-repeat. We investigated how such disease-causing mutations affect the biochemical behavior of this titin domain. All five disease-causing amino acid changes analyzed by us (p.P30068R, p.C30071R, p.W30088R, p.W30088C and p.P30091L) resulted in impaired FN3 119 domain solubility. In contrast, amino acid changes associated with common SNPs (p.V30076I, p.R30107C and p.S30125F) did not have this effect. In silica analyses further support the notion that disease-causing mutations impair proper folding of the FN3 119 domain. The results suggest that hereditary myopathy with early respiratory failure is caused by defective protein folding. (C) 2014 Elsevier B.V. All rights reserved.

Page Manager: Webmaster|Last update: 9/11/2012

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?