In addition, patients with mutations of this conserved Cx9CxnCx10C motif in COA6 protein, such as the missense mutation W59C or the nonsense mutation E87X, all had disrupted COA6 functions and subsequently developed severe mitochondrial respiratory chain disease (MRCD) with cardiac hypertrophy and HF that resulted in premature death at 1 year of age [45]. Here, COA6 is linked to hydrops fetalis.