title: Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine.
abstract: Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome.
authors: Department of Pediatrics, Division of Medical Genetics, Lucile Packard Children's Hospital, Stanford, CA 94305-5208, USA.
authors: Rachel
authors: R
authors: Cox
authors: Julia
authors: J
authors: Platt
authors: Li Chieh
authors: LC
authors: Chen
authors: Sha
authors: S
authors: Tang
authors: Lee-Jun
authors: LJ
authors: Wong
authors: Gregory M
authors: GM
authors: Enns
mesh_terms: D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007888:Leigh Disease / Q000235:genetics* / Q000473:pathology*; D007962:Leukocytes / Q000166:cytology; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012355:RNA, Transfer, Ile / Q000235:genetics*
chemical_list: D000077278:RNA, Mitochondrial; D012355:RNA, Transfer, Ile; D012313:RNA