Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.

Leigh Waddell; Michaela Kreissl; Andrew Kornberg; Paul Kennedy; Catriona Mclean; Annick Labarre-Vila; Nicole Monnier; Kathryn North; Nigel Clarke

doi:10.1016/j.nmd.2010.05.012

Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.

Leigh Waddell ^{1, 2} Michaela Kreissl ¹ Andrew Kornberg ³ Paul Kennedy ⁴ Catriona Mclean ^{4, 5} Annick Labarre-Vila ⁶ Nicole Monnier ^{7, 8} Kathryn North ^{1, 2} Nigel Clarke ^{1, 2, *}

* Auteur correspondant

1 Institute for Neuroscience and Muscle Research

2 Discipline of Paediatrics and Child Health

3 Department of Neurology

4 State Neuropathology Service, Department of Pathology

5 Department of Anatomical Pathology

6 Centre de Reference des Maladies Neuromusculaires

7 GIN - Grenoble Institut des Neurosciences

8 Laboratoire de biochimie et génétique moléculaire

Abstract : We report a third patient with typical cap myopathy due to a heterozygous TPM3 mutation, confirming the importance of this causal association. The p.R168C TPM3 mutation we identified has been reported in two previous patients. The histological changes associated with this mutation vary widely from typical cap myopathy with near complete type 1 predominance (two patients), to typical congenital fibre-type disproportion without protein inclusions (one patient). We performed 2D-gel electrophoresis using muscle biopsies from two patients with the p.R168C mutation and show that mutant protein accounts for around 50% of alpha-tropomyosin(slow) in sarcomeres, consistent with a dominant negative mechanism of disease pathogenesis.

Keywords : TPM3 Cap myopathy Congenital fibre-type disproportion Dominant negative disease

Type de document :

Article dans une revue

Neuromuscul Disord, 2010, 20 (7), pp.464-6. 〈10.1016/j.nmd.2010.05.012〉

Domaine :

Sciences du Vivant [q-bio] / Neurosciences [q-bio.NC]

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http://www.hal.inserm.fr/inserm-00589053
Contributeur : Nathalie Roux-Buisson <>
Soumis le : mercredi 13 juillet 2011 - 13:13:41
Dernière modification le : jeudi 1 février 2018 - 01:12:04

Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.

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Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3.

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