Open AccessIsolated cytochrome c oxidase deficiency as a cause of MELAS
Author(s) -
Walter Rossmanith,
Michael Freilinger,
Julia Roka,
Thomas Raffelsberger,
Karin Moser-Their,
Daniela Prayer,
G. Bernert,
Reginald E. Bittner
Publication year - 2009
Publication title -
bmj case reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.231
H-Index - 26
ISSN - 1757-790X
DOI - 10.1136/bcr.08.2008.0666
Subject(s) - frameshift mutation , cytochrome c oxidase , biology , mutation , microbiology and biotechnology , mitochondrial dna , downregulation and upregulation , protein subunit , gene , mitochondrial respiratory chain , genetics , respiratory chain , oxidase test , melas syndrome , mitochondrion , biochemistry , mitochondrial myopathy , enzyme
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.