PT - JOURNAL ARTICLE AU - Patrick M. Schaefer AU - Leonardo Scherer Alves AU - Maria Lvova AU - Jessica Huang AU - Komal Rathi AU - Kevin Janssen AU - Arrienne Butic AU - Tal Yardeni AU - Ryan Morrow AU - Marie Lott AU - Kierstin Keller AU - Benjamin A. Garcia AU - Clair A. Francomano AU - Douglas C. Wallace TI - Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree AID - 10.1101/2022.02.25.481696 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.02.25.481696 4099 - http://biorxiv.org/content/early/2022/02/25/2022.02.25.481696.short 4100 - http://biorxiv.org/content/early/2022/02/25/2022.02.25.481696.full AB - 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.Competing Interest StatementDouglas C. Wallace is part of the scientific advisory boards for: Pano Therapeutics Medical Excellence Capital. Neither of these companies have had any involvement in this research or relate to this manuscript.