title: A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia.
abstract: Autosomal dominant progressive external ophthalmoplegia is a common neurological presentation of mitochondrial disease and is characterised by multiple deletions of mitochondrial DNA in muscle. We describe a family with autosomal dominant progressive external ophthalmoplegia caused by a novel heterozygous A to C transversion at nucleotide 956 of the Twinkle gene. The deltoid muscle biopsy of the index case revealed sparse respiratory deficient cells. Multiple mitochondrial DNA deletions were clearly evident in the index case by both long-range and real-time polymerase chain reaction assays but not by Southern blotting, highlighting the diagnostic difficulties associated with characterising patients with multiple mitochondrial DNA deletions.
authors.affiliation: Department of Neurology, The Medical School, Framlington Place, University of Newcastle upon Tyne, NE2 4HH, Newcastle upon Tyne, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Deschauer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kiefer
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.forename: Langping
authors.initials: L
authors.lastname: He
authors.forename: Stephan
authors.initials: S
authors.lastname: Zierz
authors.forename: Douglass M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern / Q000379:methods; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D019915:DNA Primase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D008967:Molecular Biology / Q000379:methods; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D017246:Ophthalmoplegia, Chronic Progressive External / Q000209:etiology / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D013912:Threonine / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: C070354:Cox protein, Enterobacteria phage P2; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014764:Viral Proteins; D013912:Threonine; D019915:DNA Primase; D004265:DNA Helicases; C431576:TWNK protein, human; D008239:Lysine