A new congenital multicore titinopathy associated with fast myosin heavy chain deficiency

Aurélien Perrin, Corinne Metay, Marcello Villanova, Robert Yves Carlier, Elena Pegoraro, Raul Juntas Morales, Tanya Stojkovic, Isabelle Richard, Pascale Richard, Norma B. Romero, Henk Granzier, Michel Koenig, Edoardo Malfatti, Mireille Cossée

Research output: Contribution to journalArticle

Abstract

Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin-myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament loss. Immunohistochemistry and Western blotting revealed a marked reduction of fast myosin heavy chain isoforms. This is the first observation of a titinopathy suggesting that titin defect leads to secondary loss of fast myosin heavy chain isoforms.

Original languageEnglish (US)
Pages (from-to)846-854
Number of pages9
JournalAnnals of Clinical and Translational Neurology
Volume7
Issue number5
DOIs
StatePublished - May 1 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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    Perrin, A., Metay, C., Villanova, M., Carlier, R. Y., Pegoraro, E., Juntas Morales, R., Stojkovic, T., Richard, I., Richard, P., Romero, N. B., Granzier, H., Koenig, M., Malfatti, E., & Cossée, M. (2020). A new congenital multicore titinopathy associated with fast myosin heavy chain deficiency. Annals of Clinical and Translational Neurology, 7(5), 846-854. https://doi.org/10.1002/acn3.51031