Troponin variants in congenital myopathies: How they affect skeletal muscle mechanics

Martijn van de Locht, Tamara C. Borsboom, Josine M. Winter, Coen A.C. Ottenheijm

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. TNNC2 has been implicated in a novel congenital myopathy, TNNI2 and TNNT3 in distal arthrogryposis (DA), and TNNT1 and TNNT3 in nemaline myopathy (NEM). Variants in skeletal troponin encoding genes compromise sarcomere function, e.g., by altering the Ca2+ sensitivity of force or by inducing atrophy. Several potential therapeutic strategies are available to counter the effects of variants, such as troponin activators, introduction of wild-type protein through AAV gene therapy, and myosin modulation to improve muscle contraction. The mechanisms underlying the pathophysiological effects of the variants in skeletal troponin encoding genes are incompletely understood. Furthermore, limited knowledge is available on the structure of skeletal troponin. This review focusses on the physiology of slow and fast skeletal troponin and the pathophysiology of reported variants in skeletal troponin encoding genes. A better understanding of the pathophysiological effects of these variants, together with enhanced knowledge regarding the structure of slow and fast skeletal troponin, will direct the development of treatment strategies.

Original languageEnglish (US)
Article number9187
JournalInternational journal of molecular sciences
Volume22
Issue number17
DOIs
StatePublished - Sep 1 2021
Externally publishedYes

Keywords

  • Congenital myopathy
  • Contractility
  • Sarcomere
  • Skeletal muscle
  • Troponin

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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