title: Isolated cytochrome c oxidase deficiency as a cause of MELAS.
abstract: Deletion of a single nucleotide (7630delT) within MT-CO2, the gene of subunit II of cytochrome c oxidase (COX), was identified in a clinically typical MELAS case. The deletion-induced frameshift results in a stop codon close to the 5' end of the reading frame. The lack of subunit II (COII) precludes the assembly of COX and leads to the degradation of unassembled subunits, even those not directly affected by the mutation. Despite mitochondrial proliferation and transcriptional upregulation of nuclear and mtDNA-encoded COX genes (including MT-CO2), a severe COX deficiency was found with all investigations of the muscle biopsy (histochemistry, biochemistry, immunoblotting). The 7630delT mutation in MT-CO2 leads to a lack of COII with subsequent misassembly and degradation of respiratory complex IV despite transcriptional upregulation of its subunits. The genetic and pathobiochemical heterogeneity of MELAS appears to be greater than previously appreciated.
authors.affiliation: Medical University of Vienna, Währinger Straße 13, Vienna, 1090, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Rossmanith
authors.forename: Michael
authors.initials: M
authors.lastname: Freilinger
authors.forename: Julia
authors.initials: J
authors.lastname: Roka
authors.forename: Thomas
authors.initials: T
authors.lastname: Raffelsberger
authors.forename: Karin
authors.initials: K
authors.lastname: Moser-Their
authors.forename: Daniela
authors.initials: D
authors.lastname: Prayer
authors.forename: Günther
authors.initials: G
authors.lastname: Bernert
authors.forename: Reginald
authors.initials: R
authors.lastname: Bittner