Loading…

C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy

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...

Full description

Saved in:
Bibliographic Details
Published in:Annals of neurology 2007-04, Vol.61 (4), p.340-351
Main Authors: Carmignac, Virginie, Salih, Mustafa A. M., Quijano-Roy, Susana, Marchand, Sylvie, Al Rayess, Molham M., Mukhtar, Maowia M., Urtizberea, Jon A., Labeit, Siegfried, Guicheney, Pascale, Leturcq, France, Gautel, Mathias, Fardeau, Michel, Campbell, Kevin P., Richard, Isabelle, Estournet, Brigitte, Ferreiro, Ana
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c4229-a8f1ba8e3bd5fa5053756db16d5e4e93fdd87f105b02ccc78af95b373b92379b3
cites cdi_FETCH-LOGICAL-c4229-a8f1ba8e3bd5fa5053756db16d5e4e93fdd87f105b02ccc78af95b373b92379b3
container_end_page 351
container_issue 4
container_start_page 340
container_title Annals of neurology
container_volume 61
creator Carmignac, Virginie
Salih, Mustafa A. M.
Quijano-Roy, Susana
Marchand, Sylvie
Al Rayess, Molham M.
Mukhtar, Maowia M.
Urtizberea, Jon A.
Labeit, Siegfried
Guicheney, Pascale
Leturcq, France
Gautel, Mathias
Fardeau, Michel
Campbell, Kevin P.
Richard, Isabelle
Estournet, Brigitte
Ferreiro, Ana
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. Ann Neurol 2007;61:340–351
doi_str_mv 10.1002/ana.21089
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_19743930</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>19743930</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4229-a8f1ba8e3bd5fa5053756db16d5e4e93fdd87f105b02ccc78af95b373b92379b3</originalsourceid><addsrcrecordid>eNp1kMFu1DAQhi0EokvhwAsgX0DikNaO7dg-rlalIJVyKGi5WRPHVg1OstheSt4ew27pidNIM98_M_oQeknJGSWkPYcJzlpKlH6EVlQw2qiW68doRVjHG0EZP0HPcv5GCNEdJU_RCZWcc0HECm03TXFpDBNEXEIJEx5cdCXMU8YW9tlhwNP800XsIMWlqX1X8LjMOyi3C74L5RZ7KDVtIQ1hvp88R088xOxeHOsp-vLu4vPmfXP16fLDZn3VWN62ugHlaQ_KsX4QHupHTIpu6Gk3CMedZn4YlPSUiJ601lqpwGvRM8l63TKpe3aK3hz27tL8Y-9yMWPI1sUIk5v32VAtOdOMVPDtAbRpzjk5b3YpjJAWQ4n5Y9FUi-avxcq-Oi7d96MbHsijtgq8PgKQLUSfYLIhP3Cq01orVrnzA3cXolv-f9Gsr9f3p5tDIuTifv1LQPpuOlnlmO31pdlKdXPztRXmI_sNkTuY6g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19743930</pqid></control><display><type>article</type><title>C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy</title><source>Wiley-Blackwell Read &amp; Publish Collection</source><creator>Carmignac, Virginie ; Salih, Mustafa A. M. ; Quijano-Roy, Susana ; Marchand, Sylvie ; Al Rayess, Molham M. ; Mukhtar, Maowia M. ; Urtizberea, Jon A. ; Labeit, Siegfried ; Guicheney, Pascale ; Leturcq, France ; Gautel, Mathias ; Fardeau, Michel ; Campbell, Kevin P. ; Richard, Isabelle ; Estournet, Brigitte ; Ferreiro, Ana</creator><creatorcontrib>Carmignac, Virginie ; Salih, Mustafa A. M. ; Quijano-Roy, Susana ; Marchand, Sylvie ; Al Rayess, Molham M. ; Mukhtar, Maowia M. ; Urtizberea, Jon A. ; Labeit, Siegfried ; Guicheney, Pascale ; Leturcq, France ; Gautel, Mathias ; Fardeau, Michel ; Campbell, Kevin P. ; Richard, Isabelle ; Estournet, Brigitte ; Ferreiro, Ana</creatorcontrib><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. Ann Neurol 2007;61:340–351</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.21089</identifier><identifier>PMID: 17444505</identifier><identifier>CODEN: ANNED3</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; Age of Onset ; Biological and medical sciences ; Calpain - metabolism ; Cardiomyopathies - genetics ; Cardiomyopathies - metabolism ; Cardiomyopathies - mortality ; Cardiomyopathies - pathology ; Child ; Chromosomes, Human, Pair 2 ; Connectin ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Diseases of striated muscles. Neuromuscular diseases ; DNA Mutational Analysis ; Exons ; Family Health ; Gene Deletion ; Genetic Linkage ; Genotype ; Humans ; Male ; Medical sciences ; Molecular Sequence Data ; Muscle Proteins - chemistry ; Muscle Proteins - genetics ; Muscle Proteins - metabolism ; Muscles - pathology ; Muscles - ultrastructure ; Neurology ; Phenotype ; Protein Kinases - chemistry ; Protein Kinases - genetics ; Protein Structure, Tertiary - genetics</subject><ispartof>Annals of neurology, 2007-04, Vol.61 (4), p.340-351</ispartof><rights>Copyright © 2007 American Neurological Association</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4229-a8f1ba8e3bd5fa5053756db16d5e4e93fdd87f105b02ccc78af95b373b92379b3</citedby><cites>FETCH-LOGICAL-c4229-a8f1ba8e3bd5fa5053756db16d5e4e93fdd87f105b02ccc78af95b373b92379b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=18699983$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17444505$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carmignac, Virginie</creatorcontrib><creatorcontrib>Salih, Mustafa A. M.</creatorcontrib><creatorcontrib>Quijano-Roy, Susana</creatorcontrib><creatorcontrib>Marchand, Sylvie</creatorcontrib><creatorcontrib>Al Rayess, Molham M.</creatorcontrib><creatorcontrib>Mukhtar, Maowia M.</creatorcontrib><creatorcontrib>Urtizberea, Jon A.</creatorcontrib><creatorcontrib>Labeit, Siegfried</creatorcontrib><creatorcontrib>Guicheney, Pascale</creatorcontrib><creatorcontrib>Leturcq, France</creatorcontrib><creatorcontrib>Gautel, Mathias</creatorcontrib><creatorcontrib>Fardeau, Michel</creatorcontrib><creatorcontrib>Campbell, Kevin P.</creatorcontrib><creatorcontrib>Richard, Isabelle</creatorcontrib><creatorcontrib>Estournet, Brigitte</creatorcontrib><creatorcontrib>Ferreiro, Ana</creatorcontrib><title>C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><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. Ann Neurol 2007;61:340–351</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age of Onset</subject><subject>Biological and medical sciences</subject><subject>Calpain - metabolism</subject><subject>Cardiomyopathies - genetics</subject><subject>Cardiomyopathies - metabolism</subject><subject>Cardiomyopathies - mortality</subject><subject>Cardiomyopathies - pathology</subject><subject>Child</subject><subject>Chromosomes, Human, Pair 2</subject><subject>Connectin</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Diseases of striated muscles. Neuromuscular diseases</subject><subject>DNA Mutational Analysis</subject><subject>Exons</subject><subject>Family Health</subject><subject>Gene Deletion</subject><subject>Genetic Linkage</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Muscle Proteins - chemistry</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle Proteins - metabolism</subject><subject>Muscles - pathology</subject><subject>Muscles - ultrastructure</subject><subject>Neurology</subject><subject>Phenotype</subject><subject>Protein Kinases - chemistry</subject><subject>Protein Kinases - genetics</subject><subject>Protein Structure, Tertiary - genetics</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNp1kMFu1DAQhi0EokvhwAsgX0DikNaO7dg-rlalIJVyKGi5WRPHVg1OstheSt4ew27pidNIM98_M_oQeknJGSWkPYcJzlpKlH6EVlQw2qiW68doRVjHG0EZP0HPcv5GCNEdJU_RCZWcc0HECm03TXFpDBNEXEIJEx5cdCXMU8YW9tlhwNP800XsIMWlqX1X8LjMOyi3C74L5RZ7KDVtIQ1hvp88R088xOxeHOsp-vLu4vPmfXP16fLDZn3VWN62ugHlaQ_KsX4QHupHTIpu6Gk3CMedZn4YlPSUiJ601lqpwGvRM8l63TKpe3aK3hz27tL8Y-9yMWPI1sUIk5v32VAtOdOMVPDtAbRpzjk5b3YpjJAWQ4n5Y9FUi-avxcq-Oi7d96MbHsijtgq8PgKQLUSfYLIhP3Cq01orVrnzA3cXolv-f9Gsr9f3p5tDIuTifv1LQPpuOlnlmO31pdlKdXPztRXmI_sNkTuY6g</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>Carmignac, Virginie</creator><creator>Salih, Mustafa A. M.</creator><creator>Quijano-Roy, Susana</creator><creator>Marchand, Sylvie</creator><creator>Al Rayess, Molham M.</creator><creator>Mukhtar, Maowia M.</creator><creator>Urtizberea, Jon A.</creator><creator>Labeit, Siegfried</creator><creator>Guicheney, Pascale</creator><creator>Leturcq, France</creator><creator>Gautel, Mathias</creator><creator>Fardeau, Michel</creator><creator>Campbell, Kevin P.</creator><creator>Richard, Isabelle</creator><creator>Estournet, Brigitte</creator><creator>Ferreiro, Ana</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Willey-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>200704</creationdate><title>C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy</title><author>Carmignac, Virginie ; Salih, Mustafa A. M. ; Quijano-Roy, Susana ; Marchand, Sylvie ; Al Rayess, Molham M. ; Mukhtar, Maowia M. ; Urtizberea, Jon A. ; Labeit, Siegfried ; Guicheney, Pascale ; Leturcq, France ; Gautel, Mathias ; Fardeau, Michel ; Campbell, Kevin P. ; Richard, Isabelle ; Estournet, Brigitte ; Ferreiro, Ana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4229-a8f1ba8e3bd5fa5053756db16d5e4e93fdd87f105b02ccc78af95b373b92379b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age of Onset</topic><topic>Biological and medical sciences</topic><topic>Calpain - metabolism</topic><topic>Cardiomyopathies - genetics</topic><topic>Cardiomyopathies - metabolism</topic><topic>Cardiomyopathies - mortality</topic><topic>Cardiomyopathies - pathology</topic><topic>Child</topic><topic>Chromosomes, Human, Pair 2</topic><topic>Connectin</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Diseases of striated muscles. Neuromuscular diseases</topic><topic>DNA Mutational Analysis</topic><topic>Exons</topic><topic>Family Health</topic><topic>Gene Deletion</topic><topic>Genetic Linkage</topic><topic>Genotype</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Muscle Proteins - chemistry</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle Proteins - metabolism</topic><topic>Muscles - pathology</topic><topic>Muscles - ultrastructure</topic><topic>Neurology</topic><topic>Phenotype</topic><topic>Protein Kinases - chemistry</topic><topic>Protein Kinases - genetics</topic><topic>Protein Structure, Tertiary - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carmignac, Virginie</creatorcontrib><creatorcontrib>Salih, Mustafa A. M.</creatorcontrib><creatorcontrib>Quijano-Roy, Susana</creatorcontrib><creatorcontrib>Marchand, Sylvie</creatorcontrib><creatorcontrib>Al Rayess, Molham M.</creatorcontrib><creatorcontrib>Mukhtar, Maowia M.</creatorcontrib><creatorcontrib>Urtizberea, Jon A.</creatorcontrib><creatorcontrib>Labeit, Siegfried</creatorcontrib><creatorcontrib>Guicheney, Pascale</creatorcontrib><creatorcontrib>Leturcq, France</creatorcontrib><creatorcontrib>Gautel, Mathias</creatorcontrib><creatorcontrib>Fardeau, Michel</creatorcontrib><creatorcontrib>Campbell, Kevin P.</creatorcontrib><creatorcontrib>Richard, Isabelle</creatorcontrib><creatorcontrib>Estournet, Brigitte</creatorcontrib><creatorcontrib>Ferreiro, Ana</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carmignac, Virginie</au><au>Salih, Mustafa A. M.</au><au>Quijano-Roy, Susana</au><au>Marchand, Sylvie</au><au>Al Rayess, Molham M.</au><au>Mukhtar, Maowia M.</au><au>Urtizberea, Jon A.</au><au>Labeit, Siegfried</au><au>Guicheney, Pascale</au><au>Leturcq, France</au><au>Gautel, Mathias</au><au>Fardeau, Michel</au><au>Campbell, Kevin P.</au><au>Richard, Isabelle</au><au>Estournet, Brigitte</au><au>Ferreiro, Ana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2007-04</date><risdate>2007</risdate><volume>61</volume><issue>4</issue><spage>340</spage><epage>351</epage><pages>340-351</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><coden>ANNED3</coden><abstract>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. Ann Neurol 2007;61:340–351</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17444505</pmid><doi>10.1002/ana.21089</doi><tpages>12</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0364-5134
ispartof Annals of neurology, 2007-04, Vol.61 (4), p.340-351
issn 0364-5134
1531-8249
language eng
recordid cdi_proquest_miscellaneous_19743930
source Wiley-Blackwell Read & Publish Collection
subjects Adolescent
Adult
Age of Onset
Biological and medical sciences
Calpain - metabolism
Cardiomyopathies - genetics
Cardiomyopathies - metabolism
Cardiomyopathies - mortality
Cardiomyopathies - pathology
Child
Chromosomes, Human, Pair 2
Connectin
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Diseases of striated muscles. Neuromuscular diseases
DNA Mutational Analysis
Exons
Family Health
Gene Deletion
Genetic Linkage
Genotype
Humans
Male
Medical sciences
Molecular Sequence Data
Muscle Proteins - chemistry
Muscle Proteins - genetics
Muscle Proteins - metabolism
Muscles - pathology
Muscles - ultrastructure
Neurology
Phenotype
Protein Kinases - chemistry
Protein Kinases - genetics
Protein Structure, Tertiary - genetics
title C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T20%3A43%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=C-terminal%20titin%20deletions%20cause%20a%20novel%20early-onset%20myopathy%20with%20fatal%20cardiomyopathy&rft.jtitle=Annals%20of%20neurology&rft.au=Carmignac,%20Virginie&rft.date=2007-04&rft.volume=61&rft.issue=4&rft.spage=340&rft.epage=351&rft.pages=340-351&rft.issn=0364-5134&rft.eissn=1531-8249&rft.coden=ANNED3&rft_id=info:doi/10.1002/ana.21089&rft_dat=%3Cproquest_cross%3E19743930%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4229-a8f1ba8e3bd5fa5053756db16d5e4e93fdd87f105b02ccc78af95b373b92379b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=19743930&rft_id=info:pmid/17444505&rfr_iscdi=true