New splicing-site mutations in the SURF1 gene in Leigh syndrome patients.

TitleNew splicing-site mutations in the SURF1 gene in Leigh syndrome patients.
Publication TypeJournal Article
Year of Publication2001
AuthorsPequignot, MO, Desguerre, I, Dey, R, Tartari, M, Zeviani, M, Agostino, A, Benelli, C, Fouque, F, Prip-Buus, C, Marchant, D, Abitbol, M, Marsac, C
JournalJ Biol Chem
Date Published2001 May 04
KeywordsBase Sequence, DNA Primers, Female, Heterozygote, Homozygote, Humans, Infant, Leigh Disease, Male, Membrane Proteins, Mitochondrial Proteins, Mutation, Proteins, RNA Splicing

The gene SURF1 encodes a factor involved in the biogenesis of cytochrome c oxidase, the last complex in the respiratory chain. Mutations of the SURF1 gene result in Leigh syndrome and severe cytochrome c oxidase deficiency. Analysis of seven unrelated patients with cytochrome c oxidase deficiency and typical Leigh syndrome revealed different SURF1 mutations in four of them. Only these four cases had associated demyelinating neuropathy. Three mutations were novel splicing-site mutations that lead to the excision of exon 6. Two different novel heterozygous mutations were found at the same guanine residue at the donor splice site of intron 6; one was a deletion, whereas the other was a transition [588+1G>A]. The third novel splicing-site mutation was a homozygous [516-2_516-1delAG] in intron 5. One patient only had a homozygous polymorphism in the middle of the intron 8 [835+25C>T]. Western blot analysis showed that Surf1 protein was absent in all four patients harboring mutations. Our studies confirm that the SURF1 gene is an important nuclear gene involved in the cytochrome c oxidase deficiency. We also show that Surf1 protein is not implicated in the assembly of other respiratory chain complexes or the pyruvate dehydrogenase complex.

Alternate JournalJ. Biol. Chem.
Citation Key10.1074/jbc.M100388200
PubMed ID11279059