title: Differential features of patients with mutations in two COX assembly genes, SURF-1 and SCO2.
abstract: We screened 41 patients with undiagnosed encephalomyopathies and cytochrome c oxidase (COX) deficiency for mutations in two COX assembly genes, SURF-1 and SCO2; 6 patients had mutations in SURF-1 and 3 had mutations in SCO2. All of the mutations in SURF-1 were small-scale rearrangements (deletions/insertions); 3 patients were homozygotes and the other 3 were compound heterozygotes. 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 combination of encephalopathy and hypertrophic cardiomyopathy, and the neuropathology did not show the typical features of Leigh syndrome. In patients with SCO2 mutations, onset was earlier and the clinical course and progression to death more rapid than in patients with SURF-1 mutations. In addition, biochemical and morphological studies showed that the COX deficiency was more severe in patients with SCO2 mutations. Immunohistochemical studies suggested that SURF-1 mutations result in similarly reduced levels of mitochondrial-encoded and nuclear-encoded COX subunits, whereas SCO2 mutations affected mitochondrial-encoded subunits to a greater degree. We conclude that patients with mutations in SURF-1 and SCO2 genes have distinct phenotypes despite the common biochemical defect of COX activity.
authors.affiliation: Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Sue
authors.forename: C
authors.initials: C
authors.lastname: Karadimas
authors.forename: N
authors.initials: N
authors.lastname: Checcarelli
authors.forename: K
authors.initials: K
authors.lastname: Tanji
authors.forename: L C
authors.initials: LC
authors.lastname: Papadopoulou
authors.forename: F
authors.initials: F
authors.lastname: Pallotti
authors.forename: F L
authors.initials: FL
authors.lastname: Guo
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: D C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: R
authors.initials: R
authors.lastname: Van Coster
authors.forename: P
authors.initials: P
authors.lastname: Kaplan
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000328:Adult; D001706:Biopsy; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics; D002352:Carrier Proteins; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007888:Leigh Disease / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis / Q000235:genetics*; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D009130:Muscle, Smooth / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011506:Proteins; C400285:SCO2 protein, human; C092928:Surf-1 protein