Researchers have identified novel genetic variants that cause congenital myopathy, and a potential treatment strategy for overcoming it.
“Troponin C (TnC) is a critical regulator of skeletal muscle contraction,” said Dr Martijn van de Locht of Amsterdam UMC in Amsterdam, the Netherlands. “Surprisingly, the gene encoding fast skeletal TnC (TNNC2) has never been implicated in muscle disease.”
At WMS 2020, Dr van de Locht presented findings on two families with pathogenic variants in TNNC2. Affected patients had congenital muscle disease, characterized by muscle weakness, poor muscle contractility, and difficulty breathing.
Using molecular simulation models, the researchers showed that the 2 pathogenic variants, c.100G>T and c.237G>C, disrupt TnC binding sites for calcium and troponin I, respectively. Both variants result in myocytes with markedly reduced calcium sensitivity.