New Splicing-site Mutations in the SURF1Gene in Leigh Syndrome Patients

• Published in: The Journal of biological chemistry 2001-01, Vol.276 (18), p.15326-15329
• Main Authors: Péquignot, Marie O., Desguerre, Isabelle, Dey, Runu, Tartari, Marzia, Zeviani, Massimo, Agostino, Alessandro, Benelli, Chantal, Fouque, Françoise, Prip-Buus, Carina, Marchant, Dominique, Abitbol, Marc, Marsac, Cécile
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M100388200

The gene SURF1 encodes a factor involved in the biogenesis of cytochrome c oxidase, the last complex in the respiratory chain. Mutations of theSURF1 gene result in Leigh syndrome and severe cytochromec 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 theSURF1 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.