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

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.

• Authors: 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
• Journal: Annals of clinical and translational neurology (Ann Clin Transl Neurol) Vol. 7 Issue 5 Pg. 846-854 (05 2020) ISSN: 2328-9503 [Electronic] United States
• PMID: 32307885 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Chemical References

• Connectin
• TTN protein, human
• Myosin Heavy Chains

Topics

• Adolescent
• Child
• Connectin (genetics)
• Deltoid Muscle (pathology)
• Female
• Humans
• Male
• Muscular Diseases (congenital, genetics, metabolism, pathology)
• Myosin Heavy Chains (deficiency)
• Pedigree
• Siblings