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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Titinopathies: what happens when a big gene mutates in a big family?

In this issue of Neurology, Udd et al.1 add another chapter to the evolving story of titinopathies by investigating the skeletal muscle disease that is now also known to be a titinopathy in a multigeneration consanguineous family off the west coast of Finland.

Removal of the calpain 3 protease reverses the myopathology in a mouse model for titinopathies.

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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.

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Secondary calpain3 deficiency in 2q-linked muscular dystrophy

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