NO MITOCHONDRIAL CYTOCHROME-OXIDASE (COX) GENE-MUTATIONS IN 18 CASES OF COX DEFICIENCY

Cytochrome c oxidase (COX) deficiency causes a variety of neuromuscula r and non-neuromuscular disorders in childhood and adulthood and can t heoretically undergo either a nuclear or a mitochondrial (mt) mode of inheritance, making genetic counseling in COX deficiency particularly hazardous. In an attempt to determine the respective roles of mtDNA an d nuclear DNA mutations in COX deficiency, we sequenced the three mito chondrially encoded COX subunits (COXI-III) in a series of 18 patients with isolated COX deficiency, especially as COXI-III code for the cat alytic site of the enzyme. We failed to detect any deleterious mutatio ns in this series. Moreover, no mtDNA deletion was observed and sequen cing of the flanking tRNA genes involved in the maturation of the COX transcripts failed to detect deleterious mutations as well. The presen t study supports the view that the disease-causing mutations do not li e in the mt genome but, rather, in the nuclear genes encoding either t he COX subunits or the proteins involved in assembly of the complex an d suggests a recurrent risk of 25% rather than other modes of inherita nce in COX deficiencies.