A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia.
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.
Deschauer
Marcus
M
Department of Neurology, The Medical School, Framlington Place, University of Newcastle upon Tyne, NE2 4HH, Newcastle upon Tyne, UK.
Kiefer
Reinhard
R
Blakely
Emma L
EL
He
Langping
L
Zierz
Stephan
S
Turnbull
Douglass M
DM
Taylor
Robert W
RW
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
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