title: [A new missense mutation of 574C>T in the SURF1 gene--biochemical and molecular genetic study in seven children with Leigh syndrome].
abstract: BACKGROUND
  Leigh disease, subacute necrotizing encephalopathy, is a serious mitochondrial disorder of energy-providing metabolism. Clinical presentation usually starts in infancy as a progressive neurodegenerative disorder with retardation and regression of psychomotor development. The most common form of the disease is associated with deficiency of the cytochrome c oxidase (COX) due to SURF1 gene mutations. SURF1 encodes an inner mitochondrial membrane protein involved in the biogenesis and assembly of COX complex.
  
  
  RESULTS
  The activities of mitochondrial respiratory chain complexes were determined spectrophotometrically in isolated lymphocytes, platelets, muscle mitochondria and cultured fibroblasts. Generalised decrease of COX activity was found in 7 children with typical symptoms of Leigh disease. Two-dimensional electrophoresis of mitochondrial proteins showed altered assembly pattern of COX. As demonstrated by Western blot analysis of mitochondria or mitoplasts with anti-hSurf1 antibodies (gift from Dr. E. A. Shoubridge), the Surf1 protein was absent in all 5 investigated patients. Molecular analyses in the 7 patients revealed the presence of mutations in the SURF1 gene--six patients harboured previously described SURF1 mutations, a new mutation 574C > T was found in one patient.
  
  
  CONCLUSIONS
  The co-operation among the patient's families, clinicians and specialised laboratories is essential for the diagnostic of mitochondrial disorders. The treatment of Leigh syndrome is only symptomatic and the prognosis of the disease is unfavourable. The diagnostics on biochemical and molecular level is necessary for genetic counselling and prenatal diagnosis in affected families.
authors.affiliation: Klinika dĕtského a dorostového lékarství a Centrum integrované genomiky 1. LF UK a VFN, Praha.
authors.forename: M
authors.initials: M
authors.lastname: Capková
authors.forename: H
authors.initials: H
authors.lastname: Hansíková
authors.forename: C
authors.initials: C
authors.lastname: Godinot
authors.forename: H
authors.initials: H
authors.lastname: Houst'ková
authors.forename: J
authors.initials: J
authors.lastname: Houstĕk
authors.forename: J
authors.initials: J
authors.lastname: Zeman
mesh_terms: D002648:Child; D003576:Electron Transport Complex IV / Q000235:genetics; D006801:Humans; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020125:Mutation, Missense; D011506:Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C092928:Surf-1 protein; D003576:Electron Transport Complex IV