title: New mitochondrial tRNA HIS mutation in a family with lactic acidosis and stroke-like episodes (MELAS).
abstract: We report a new mutation in m.12146 A>G in the mt-tRNA(His) in a family with a remarkable clinical history having different degrees of lactic acidosis and stroke-like episodes. Biochemical measurements of a muscle biopsy established an isolated complex IV deficiency, while similar analysis of fibroblasts showed a combined complex I,III and IV deficiency. Transmitochondrial cybrid analysis proved that this tRNA(His) mutation causes the enzymatic deficiency. This family illustrates the complexity of the clinical, biochemical and genetic characteristics of a novel mtDNA encoded disorder, as well as the challenge to prove its pathogenicity.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Calvaruso
authors.forename: Michel A
authors.initials: MA
authors.lastname: Willemsen
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: Mariël
authors.initials: M
authors.lastname: van den Brand
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Leo
authors.initials: L
authors.lastname: Nijtmans
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001921:Brain / Q000473:pathology*; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D045222:Electron Transport Chain Complex Proteins / Q000172:deficiency; D057075:Enzyme Assays; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D017241:MELAS Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D012354:RNA, Transfer, His / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; D012354:RNA, Transfer, His; D011451:Prostaglandin-Endoperoxide Synthases