Titinopathies and extension of the M-line mutation phenotype beyond distal myopathy and LGMD2J

  title={Titinopathies and extension of the M-line mutation phenotype beyond distal myopathy and LGMD2J},
  author={Bjarne Udd and Anna Vihola and Jaakko Sarparanta and Isabelle Richard and Peter Hackman},
  pages={636 - 642}
Objective: To determine the phenotype variability associated with the specific C-terminal M-line titin mutation known to cause autosomal dominant distal myopathy, tibial muscular dystrophy (TMD; MIM 600334), and limb girdle muscular dystrophy 2J (LGMD2J). Methods: Three hundred eighty-six individuals were genotyped for the Finnish founder mutation in titin (FINmaj) causing TMD/LGMD2J. Results: Two hundred seven patients were heterozygous for the mutation. Among these patients, 189 (91%) had a… 

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Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD)


Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin.
Immunohistochemical analysis using two exon-specific antibodies directed to the M-line region of titin demonstrated the specific loss of carboxy-terminal titin epitopes in the TMD muscle samples that were studied, thus implicating a functional defect of theM-line titin in the genesis of the T MD disease phenotype.
Assignment of the tibial muscular dystrophy locus to chromosome 2q31.
The disease locus that was found represents a novel muscular dystrophy locus, providing evidence for the involvement of one additional gene in the distal myopathy group of muscle disorders.
The muscular dystrophy with myositis (mdm) mouse mutation disrupts a skeletal muscle-specific domain of titin.
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Muscular dystrophy with separate clinical phenotypes in a large family
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