Reduction in mitochondrial DNA copy number in peripheral leukocytes after onset of Huntington's disease.
Huntington's disease (HD) is an inherited neurodegenerative disorder characterised by movement disorder, cognitive symptoms and psychiatric symptoms with predominantly adult-onset. The mutant huntingtin protein leads to mitochondrial dysfunction in blood leukocytes. This discovery led to the investigation of the mitochondrial DNA (mtDNA) copy number relative to nuclear DNA (nDNA) in leukocytes from carriers of the HD mutation compared to healthy individuals. We found significantly reduced mtDNA/nDNA in HD mutation carriers compared to controls. A longitudinal study of archive DNA sample pairs from HD patients revealed a biphasic pattern of increasing mtDNA/nDNA before onset of motor symptoms and decreasing mtDNA/nDNA after.
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Maria Hvidberg
MH
Petersen
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Esben
E
Budtz-Jørgensen
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Sven Asger
SA
Sørensen
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark; Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
Jørgen Erik
JE
Nielsen
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark; Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
Lena Elisabeth
LE
Hjermind
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark; Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
Tua
T
Vinther-Jensen
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Signe Marie Borch
SM
Nielsen
Department of Cellular and Molecular Medicine, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. Electronic address: annenoe@sund.ku.dk.
Anne
A
Nørremølle
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002648:Child; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000235:genetics; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D007962:Leukocytes / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D004272:DNA, Mitochondrial
Biphasic; Huntington's disease; Mitochondrial DNA copy number