Troponin Variants in Congenital Myopathies: How They Affect Skeletal Muscle Mechanics
The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. <i>TNNC2</i> has been implicated in a novel congenital myopathy, <i>TNNI2</i> and <i>TNNT3</i> in distal arthrogry...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/17/9187 |
| Summary: | The troponin complex is a key regulator of muscle contraction. Multiple variants in skeletal troponin encoding genes result in congenital myopathies. <i>TNNC2</i> has been implicated in a novel congenital myopathy, <i>TNNI2</i> and <i>TNNT3</i> in distal arthrogryposis (DA), and <i>TNNT1</i> and <i>TNNT3</i> in nemaline myopathy (NEM). Variants in skeletal troponin encoding genes compromise sarcomere function, e.g., by altering the Ca<sup>2+</sup> 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. |
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| ISSN: | 1661-6596 1422-0067 |