Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185 of mitochondrial DNA.

Article Details


Castagna AE, Addis J, McInnes RR, Clarke JT, Ashby P, Blaser S, Robinson BH

Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185 of mitochondrial DNA.

Am J Med Genet A. 2007 Apr 15;143A(8):808-16.

PubMed ID
17352390 [ View in PubMed

A T-to-C missense mutation at nucleotide position 9,185 in the protein-coding ATP6 gene of the mitochondrial genome was present at high heteroplasmy in members of a Canadian family with Leigh syndrome with predominant ataxia and peripheral neuropathy. This mutation results in the substitution of a proline residue for an evolutionary-conserved leucine at position of amino acid 220 near the carboxyl terminus of the mitochondrial protein. The index patient and brother, who had an identical clinical presentation, had >90% mutant mtDNA in cultured skin fibroblasts, lymphocytes, and whole blood. Their mother and a maternal uncle, symptomatic with a peripheral neuropathy alone, had 86% and 85% heteroplasmy, respectively. Symptomatic maternal cousins with early onset revealed 90% and 91% mutant mtDNA in all tissues analyzed. Studies of lymphoblasts from the asymptomatic maternal grandmother and eldest brother of the proband were heteroplasmic for mutant mtDNA with 56% and 17%, respectively. Biochemical analysis demonstrated normal respiratory chain enzyme activity in muscle and fibroblasts, normal ATP synthesis, but reduced oligomycin-sensitive H(+)ATPase in cultured lymphoblast mitochondria. We propose that the 9,185T > C mtDNA mutation is pathogenic even though the initial phenotype is mild and the biochemical phenotype not easily detectable.

DrugBank Data that Cites this Article

NameUniProt ID
ATP synthase subunit aP00846Details