A new mutation in one of the components of the complex IV of the respiratory chain responsible for MELAS syndrome

MELAS syndrome is one of the mitochondrial diseases described mainly in adults. As its acronym suggests, it combines myopathy (M), encephalopathy (E), lactic acidosis (LA) and pseudo-stroke (S). To this complex and protean picture can be added cardiac complications of various types (abnormalities of myocardial contractility, conduction disorders, etc.). MELAS syndrome is transmitted by maternal inheritance and is due in the vast majority of cases to a one-time abnormality in the mitochondrial DNA (the 3243A> G mutation) encoding a transfer RNA. Most of the time, these are sporadic cases. 

In an article published in May 2021, Chinese clinicians associated with German geneticists report the observation of a young 12-year-old patient fulfilling all the diagnostic criteria in favor of a MELAS syndrome but whose genotype was found to be unprecedented. The sequencing of its mitochondrial DNA has indeed revealed the presence of a pathogenic variant in the MT-CO3 gene encoding one of the sub-elements of complex IV of the respiratory chain. Mutations in genes encoding complex proteins are exceptional. In the present case, additional functional studies, in particular from the study of cybrids, were necessary to confirm the pathogenicity of the variant.


Identification of a Novel Variant in MT-CO3 Causing MELAS. Xu M, Kopajtich R, Elstner M, Wang Z et al. Front Genet. 2021 (Mai).12:638749.