Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy
Annals of Neurology, Volume 61, No. 4, Year 2007
Notification
URL copied to clipboard!
Description
Objective: The giant protein titin is essential for striated muscle development, structure, and elasticity. All titin mutations reported to date cause late-onset, dominant disorders involving either skeletal muscle or the heart. Our aim was to delineate the phenotype and determine the genetic defects in two consanguineous families with an early-onset, recessive muscle and cardiac disorder. Methods: Clinical and myopathological reevaluation of the five affected children, positional cloning, immunofluorescence, and Western blot studies were performed. Results: All children presented with congenital muscle weakness and childhood-onset fatal dilated cardiomyopathy. Skeletal muscle biopsies showed minicores, centrally located nuclei, and/or dystrophic lesions. In each family, we identified a homozygous titin deletion in exons encoding the C-terminal M-line region. Both deletions cause a frameshift downstream of the titin kinase domain and protein truncation. Immunofluorescence confirmed that truncated titins lacking the C-terminal end were incorporated into sarcomeres. Calpain 3 was secondarily depleted. Interpretation: M-line titin homozygous truncations cause the first congenital and purely recessive titinopathy, and the first to involve both cardiac and skeletal muscle. These results expand the spectrum of early-onset myopathies and suggest that titin segments downstream of the kinase domain are dispensable for skeletal and cardiac muscle development, but are crucial for maintaining sarcomere integrity. © 2007 American Neurological Association.
Authors & Co-Authors
Carmignac, Virginie
Unknown Affiliation
Salih, Mustafa Abdalla M.
Unknown Affiliation
Quijano-Roy, Susana
Unknown Affiliation
Marchand, Sylvie
Unknown Affiliation
Al Rayess, M.
Unknown Affiliation
Mukhtar, Maowia Mohamed
Unknown Affiliation
Urtizberea, Jean Andoni M.
Unknown Affiliation
Labeit, Siegfried
Unknown Affiliation
Guicheney, Pascale
Unknown Affiliation
Leturcq, France
Unknown Affiliation
Gautel, Mathias
Unknown Affiliation
Fardeau, Michael
Unknown Affiliation
Campbell, Kevin P.
Unknown Affiliation
Richard, I.
Unknown Affiliation
Estournet-Mathiaud, Brigitte
Unknown Affiliation
Ferreiro, Ana
Unknown Affiliation
Statistics
Citations: 222
Authors: 16
Affiliations: 12
Identifiers
Doi:
10.1002/ana.21089
ISSN:
03645134
Research Areas
Genetics And Genomics
Maternal And Child Health
Noncommunicable Diseases