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Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree

Schaefer, P. M.; Scherer Alves, L.; Lvova, M.; Huang, J.; Rathi, K.; Janssen, K.; Butic, A.; Yardeni, T.; Morrow, R.; Lott, M.; Keller, K.; Garcia, B.; Francomano, C. A.; Wallace, D. C.

2022-02-25 genetics
10.1101/2022.02.25.481696 bioRxiv
Show abstract

Mitochondrial dysfunction is associated with a range of clinical manifestations including neuropsychiatric and metabolic disorder. Here, we reanalyzed a family with an L-Histidine Decarboxylase (HDC) variant previously linked to Tourette syndrome but with associated connective tissue and metabolic features of unknown etiology. We identified a mitochondrial haplogroup J-defining mutation on the haplogroup H background that functionally interacts with the L-Histidine Decarboxylase variant via calcium homeostasis. Our findings establish how a common mtDNA variant on a different mtDNA background can result in mitochondrial dysfunction, demonstrate a role for histaminergic signaling in modifying mitochondrial phenotypes, and link mitochondria dysfunction to connective tissue phenotypes.

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