RT Journal Article
SR Electronic
T1 Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.25.481696
DO 10.1101/2022.02.25.481696
A1 Patrick M. Schaefer
A1 Leonardo Scherer Alves
A1 Maria Lvova
A1 Jessica Huang
A1 Komal Rathi
A1 Kevin Janssen
A1 Arrienne Butic
A1 Tal Yardeni
A1 Ryan Morrow
A1 Marie Lott
A1 Kierstin Keller
A1 Benjamin A. Garcia
A1 Clair A. Francomano
A1 Douglas C. Wallace
YR 2022
UL http://biorxiv.org/content/early/2022/02/25/2022.02.25.481696.abstract
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.