Differential features of patients with mutations in two COX assembly genes, SURF-1 and SCO2

We screened 41 patients with undiagnosed encephalomyopathies and cytochrome E oxidase (COX) deficiency for mutations in two COX assembly genes, SURF-I and SCO2; 6 patients had mutations in SURF-I and 3 had mutations in SCO2. All of the mutations in SURF-I were small-scale rearrangements (deletions/i nsertions); 3 patients were homozygotes and the other 3 were compound heter ozygotes. All patients with SCO2 mutations were compound heterozygotes for nonsense or missense mutations. All of the patients with mutations in SURF- 1 had Leigh syndrome, whereas the 3 patients with SCO2 mutations had a comb ination of encephalopathy and hypertrophic cardiomyopathy, and the neuropat hology did not show the typical features of Leigh syndrome. In patients wit h SCO2 mutations, onset was earlier and the clinical course and progression to death more rapid than in patients with SURF-I mutations. In addition, b iochemical and morphological studies showed that the COX deficiency was mor e severe in patients with SCO2 mutations. Immunohistochemical studies sugge sted that SURF-I mutations result in similarly reduced levels of mitochondr ial-encoded and nuclear-encoded COX subunits, whereas SCO2 mutations affect ed mitochondrial-encoded subunits to a greater degree. We conclude that pat ients with mutations in SURF-I and SCO2 genes have distinct phenotypes desp ite the common biochemical defect of COX activity.