Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. |
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| Authors: | V Tiranti K Hoertnagel R Carrozzo C Galimberti M Munaro M Granatiero L Zelante P Gasparini R Marzella M Rocchi M P Bayona-Bafaluy J A Enriquez G Uziel E Bertini C Dionisi-Vici B Franco T Meitinger and M Zeviani |
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| Institution: | 1Istituto Nazionale Neurologico “Carlo Besta”;2Téléthon Institute for Genetics and Medicine, Milan;3Abteilung Medizinische Genetik, Kinderklinik der Ludwig-Maximilians Universität München, Munich;4Ospedale Pediatrico “Bambino Gesù,” Rome;5Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Italy;6Università Statale di Bari, Bari, Italy;7Universidad de Zaragoza, Zaragoza, Spain |
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| Abstract: | Leigh disease associated with cytochrome c oxidase deficiency (LDCOX-]) is one of the most common disorders of the mitochondrial respiratory chain, in infancy and childhood. No mutations in any of the genes encoding the COX-protein subunits have been identified in LD(COX-) patients. Using complementation assays based on the fusion of LD(COX-) cell lines with several rodent/human rho0 hybrids, we demonstrated that the COX phenotype was rescued by the presence of a normal human chromosome 9. Linkage analysis restricted the disease locus to the subtelomeric region of chromosome 9q, within the 7-cM interval between markers D9S1847 and D9S1826. Candidate genes within this region include SURF-1, the yeast homologue (SHY-1) of which encodes a mitochondrial protein necessary for the maintenance of COX activity and respiration. Sequence analysis of SURF-1 revealed mutations in numerous DNA samples from LD(COX-) patients, indicating that this gene is responsible for the major complementation group in this important mitochondrial disorder. |
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| Keywords: | Author Keywords: Leigh disease Cytochrome c oxidase Mitochondrial disorder Cell complementation Somatic cell hybrids Rho0 cells |
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