Discordant Monozygotic Parkinson Disease Twins: Role of Mitochondrial Integrity

Marija Dulovic-Mahlow, Inke R. König, Joanne Trinh, Sokhna Haissatou Diaw, Peter P. Urban, Evelyn Knappe, Neele Kuhnke, Lena Christin Ingwersen, Frauke Hinrichs, Joachim Weber, Patrycja Kupnicka, Alexander Balck, Sylvie Delcambre, Tillman Vollbrandt, Anne Grünewald, Christine Klein, Philip Seibler, Katja Lohmann*

*Corresponding author for this work


Objective: Even though genetic predisposition has proven to be an important element in Parkinson's disease (PD) etiology, monozygotic (MZ) twins with PD displayed a concordance rate of only about 20% despite their shared identical genetic background. Methods: We recruited 5 pairs of MZ twins discordant for idiopathic PD and established skin fibroblast cultures to investigate mitochondrial phenotypes in these cellular models against the background of a presumably identical genome. To test for genetic differences, we performed whole genome sequencing, deep mitochondrial DNA (mtDNA) sequencing, and tested for mitochondrial deletions by multiplex real-time polymerase chain reaction (PCR) in the fibroblast cultures. Further, the fibroblast cultures were tested for mitochondrial integrity by immunocytochemistry, immunoblotting, flow cytometry, and real-time PCR to quantify gene expression. Results: Genome sequencing did not identify any genetic difference. We found decreased mitochondrial functionality with reduced cellular adenosine triphosphate (ATP) levels, altered mitochondrial morphology, elevated protein levels of superoxide dismutase 2 (SOD2), and increased levels of peroxisome proliferator-activated receptor-gamma coactivator-α (PPARGC1A) messenger RNA (mRNA) in skin fibroblast cultures from the affected compared to the unaffected twins. Further, there was a tendency for a higher number of somatic mtDNA variants among the affected twins. Interpretation: We demonstrate disease-related differences in mitochondrial integrity in the genetically identical twins. Of note, the clinical expression matches functional alterations of the mitochondria. ANN NEUROL 2021;89:158–164.

Original languageEnglish
JournalAnnals of Neurology
Issue number1
Pages (from-to)158-164
Number of pages7
Publication statusPublished - 01.2021

Research Areas and Centers

  • Research Area: Medical Genetics


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