title: New phenotypic diversity associated with the mitochondrial tRNA(SerUCN) gene mutation.
abstract: We performed detailed clinical, histopathological, biochemical, in vitro translation and molecular genetic analysis in patients from two unrelated families harbouring the tRNA(SerUCN) 7472C-insertion mutation. Proband 1 developed a progressive neurodegenerative phenotype characterised by myoclonus, epilepsy, cerebellar ataxia and progressive hearing loss. Proband 2 had a comparatively benign phenotype characterised by isolated myopathy with exercise intolerance. Both patients had the 7472C-insertion mutation in identical proportions and they exhibited a similar muscle biochemical and histopathological phenotype. However, proband 2 also had a previously unreported homoplasmic A to C transition at nucleotide position 7472 in the tRNA(SerUCN) gene. This change lengthens further the homopolymeric C run already expanded by the 7472C-insertion. These data extend the phenotypic range associated with the 7472C-insertion to include isolated skeletal myopathy, as well as a MERRF-like phenotype.
authors.affiliation: Centre for Neuromuscular Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: T
authors.initials: T
authors.lastname: Pulkes
authors.forename: D
authors.initials: D
authors.lastname: Liolitsa
authors.forename: L H
authors.initials: LH
authors.lastname: Eunson
authors.forename: M
authors.initials: M
authors.lastname: Rose
authors.forename: I P
authors.initials: IP
authors.lastname: Nelson
authors.forename: S
authors.initials: S
authors.lastname: Rahman
authors.forename: J
authors.initials: J
authors.lastname: Poulton
authors.forename: D R
authors.initials: DR
authors.lastname: Marchington
authors.forename: D N
authors.initials: DN
authors.lastname: Landon
authors.forename: A G
authors.initials: AG
authors.lastname: Debono
authors.forename: J A
authors.initials: JA
authors.lastname: Morgan-Hughes
authors.forename: M G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004586:Electrophoresis / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008931:Mitochondria, Muscle / Q000473:pathology; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D009690:Nucleic Acid Conformation; D010641:Phenotype; D012362:RNA, Transfer, Ser / Q000737:chemistry / Q000235:genetics*; D012694:Serine / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012362:RNA, Transfer, Ser; D012694:Serine; D003576:Electron Transport Complex IV