title: Mutation in the mitochondrial tRNA(Val) causes mitochondrial encephalopathy, lactic acidosis and stroke-like episodes.
abstract: An m.1630A>G mutation in the mitochondrial tRNA(Val) (MTTV) was identified in a patient with hearing impairment, short stature and new onset of stroke. This mutation has previously been identified in a patient with the mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE). The mother of the proband also had high levels of the m.1630A>G allele present in blood and other tissues, without symptoms. To confirm the pathogenicity of this mutation, we created cybrid cell lines with various mutation loads. The m.1630A>G mutation impairs oxygen consumption, affects the stability of the MTTV and reduces the levels of subunits of the electron transport chain.
authors.affiliation: Section of Biochemical Genetics, The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA. glatzc@email.chop.edu
authors.forename: Catherine
authors.initials: C
authors.lastname: Glatz
authors.forename: Kristin
authors.initials: K
authors.lastname: D'Aco
authors.forename: Sabrina
authors.initials: S
authors.lastname: Smith
authors.forename: Neal
authors.initials: N
authors.lastname: Sondheimer
mesh_terms: D000293:Adolescent; D000483:Alleles; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D004579:Electron Transport; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009690:Nucleic Acid Conformation; D010100:Oxygen / Q000378:metabolism; D017354:Point Mutation; D012366:RNA, Transfer, Val / Q000235:genetics* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D012366:RNA, Transfer, Val; D010100:Oxygen