title: Two novel mutations of SURF1 in Leigh syndrome with cytochrome c oxidase deficiency.
abstract: Cytochrome c oxidase (COX) deficiency is the most common cause of Leigh syndrome (LS). COX consists of ten nuclear-encoded and three mtDNA-encoded structural subunits. Although the nucleotide sequences of all 13 genes are known, no mutation was found in nuclear-encoded subunit genes of COX-deficiency patients. Zhu et al. (1998) and Tiranti et al. (1998) found nine mutations in the surfeit 1 (SURF1) gene in LS families with COX deficiency. The mouse surfeit gene cluster consists of six closely spaced housekeeping genes unrelated by sequence homology. Except for the Surf3 gene, the function is still not known. The juxtaposition of at least five of the surfeit genes is conserved between birds and mammals. We identified two novel mutations of SURF1 in a Japanese LS patient with COX deficiency using direct sequencing analysis. Firstly, a 2-bp deletion at nucleotide position 790 (790delAG) in exon 8 was found, which shifts the reading frame such that the mutant protein has a completely different amino acid sequence from codon 264 to the premature stop codon at 290. Secondly, we found a T-to-G transversion at nucleotide 820, resulting in the substitution of tyrosine by aspartic acid at codon 274 (Y274D). We also studied the parents' genes, and found that the Y274D mutation was in his father and the 790delAG mutation was in his mother heterozygously. Therefore, we concluded that the patient was a compound heterozygote with these mutations. These are the first pathogenetic SURF1 mutations identified in a Japanese family.
authors.affiliation: Department of Pediatrics, Okayama University Medical School, Japan. asd@med.okayama-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Teraoka
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: S
authors.initials: S
authors.lastname: Ninomiya
authors.forename: C
authors.initials: C
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
mesh_terms: D019943:Amino Acid Substitution; D001706:Biopsy; D030401:Cytochrome-c Oxidase Deficiency; D005091:Exons; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D007888:Leigh Disease / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C092928:Surf-1 protein