Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency

At least three proteins, COX17p, SCO1p, and its homologue SCO2p are thought to be involved in mitochondrial copper transport to cytochrome-c-oxidase ( COX), the terminal enzyme of the respiratory chain. Recently, we and others have shown that mutations in SCO2 are associated with a lethal infantile h ypertrophic cardiomyopathy (HCMP) with COX-deficiency. The majority of pati ents with a similar phenotype were, however, negative for SCO2 mutations, s uggesting the other genes as candidates for this disorder. Here we report o n the genomic organization of SCO1 and COX17 on human chromosomes 17 and 3 respectively, and the complete sequence analysis of COX17 and SCO1 in 30 pa tients with COX deficiency. Using a panel of human:mouse-monochromosomal hy brids, the expression of COX17 was specifically restricted to chromosome 3, indicating that the previously reported sequence on chromosome 13 represen ts a pseudogene. DNA sequence analysis of SCO1 and COX17 in nine patients w ith severe COX deficiency and fatal HCMP, and in 21 patients with other COX deficiency disorders, did not reveal any pathogenic mutations or polymorph isms. We conclude that neither SCO1 nor COX17 are common causes of COX defi ciency disorders. (C) 2000 Academic Press.