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

@article{Carmignac2007CterminalTD,
  title={C‐terminal titin deletions cause a novel early‐onset myopathy with fatal cardiomyopathy},
  author={Virginie Carmignac and Mustafa A. M. Salih and S. Quijano-roy and Sylvie Marchand and M Al Rayess and Maowia M. Mukhtar and J Andoni Urtizberea and Siegfried Labeit and Pascale Guicheney and France Leturcq and Mathias Gautel and Michel Gustave Jules Fardeau and Kevin P. Campbell and Isabelle Richard and Brigitte Estournet and Ana Ferreiro},
  journal={Annals of Neurology},
  year={2007},
  volume={61}
}
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. 
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211 Citations
Highly Influential Citations
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211 Citations

Atypical phenotypes in titinopathies explained by second titin mutations
TLDR
This study aimed to clarify the molecular cause of the variant phenotypes in 8 patients of 7 European families with previously reported titin gene (TTN) mutations causing tibial muscular dystrophy.
Novel heterozygous truncating titin variants affecting the A‐band are associated with cardiomyopathy and myopathy/muscular dystrophy
TLDR
Recent reports show pathogenic variants in TTN may result in a broader phenotypic spectrum than previously recognized, and this work is the first to show this.
Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD)
A ‘second truncation’ in TTN causes early onset recessive muscular dystrophy
Myopathies caused by homozygous titin mutations: limb-girdle muscular dystrophy 2J and variations of phenotype
TLDR
A French family with an autosomal-dominant late-onset distal myopathy of the tibial muscular dystrophy phenotype segregating in several members of the family was described and the early phenotype in a newly identified young patient with homozygous Finnish C-terminal titin mutation (FINmaj) was detailed.
Titin in muscular dystrophy and cardiomyopathy: Urinary titin as a novel marker.
Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies.
TLDR
By crossing the FINmaj model with a calpain 3-deficient model, the TMD phenotype was corrected, demonstrating a participation of cal pain 3 in the pathogenesis of this disease.
The first Italian family with tibial muscular dystrophy caused by a novel titin mutation
TLDR
Since the introduction of a proline in the last domain of titin was previously known to cause TMD in French families, it can conclude that this missense mutation is the obvious pathogenetic mutation in the affected patients.
Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin.
TLDR
A novel and the first disease-causing mutation in A-band titin associated with hereditary myopathy with early respiratory failure is demonstrated and the typical histopathological features with prominent myofibrillar lesions and inclusions in muscle and respiratory failure early in the clinical course should be incentives for analysis of TTN mutations.
Adult onset limb-girdle muscular dystrophy — A recessive titinopathy masquerading as myositis
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TLDR
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TLDR
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TLDR
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