To test the hypothesis that the SCO2 mutation is associated with mitochondrial abnormalities, and intracellular Ca<sup>2+</sup> -overload resulting in functional derangements and arrhythmias, we investigated in SCO2-mutated iPSC-CMs (compared to control cardiomyocytes): (i) the ultrastructural changes; (ii) the inotropic responsiveness to β-adrenergic stimulation, increased [Ca<sup>2+</sup> ]<sub>o</sub> and angiotensin-II (AT-II); and (iii) the Beat Rate Variability (BRV) characteristics.
Our observations confirm that mutations in the SCO2 gene are frequently associated with the neurogenic pattern of skeletal muscle involvement accompanied by mitochondrial abnormalities.