title: Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT.
abstract: Exome sequencing identified compound heterozygous mutations in the recently discovered mitochondrial methionyl-tRNA formyltransferase (MTFMT) gene in two sisters with mild Leigh syndrome and combined respiratory chain deficiency. The mutations lead to undetectable levels of the MTFMT protein. Blue native polyacrylamide gel electrophoresis showed decreased complexes I and IV, and additional products stained with complex V antibodies, however the overall steady state level of mt-tRNA(Met) was normal. Our data illustrate that exome sequencing is an excellent diagnostic tool, and its value in clinical medicine is enormous, however it can only be optimally exploited if combined with detailed phenotyping and functional studies.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Vivienne C M
authors.initials: VC
authors.lastname: Neeve
authors.forename: Angela
authors.initials: A
authors.lastname: Pyle
authors.forename: Veronika
authors.initials: V
authors.lastname: Boczonadi
authors.forename: Aurora
authors.initials: A
authors.lastname: Gomez-Duran
authors.forename: Helen
authors.initials: H
authors.lastname: Griffin
authors.forename: Mauro
authors.initials: M
authors.lastname: Santibanez-Koref
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gaiser
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzschach
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D004579:Electron Transport / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D035781:Siblings
chemical_list: D017931:DNA Primers
keywords: Leigh syndrome; Mitochondrial encephalomyopathy; Mitochondrial translation; mt-tRNA modification