Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree

Patrick M. Schaefer, Leonardo Scherer Alves, Maria Lvova, Jessica Huang, Komal Rathi, Kevin Janssen, Arrienne Butic, Tal Yardeni, Ryan Morrow, Marie Lott, Kierstin Keller, Benjamin A. Garcia, Clair A. Francomano, Douglas C. Wallace
doi: https://doi.org/10.1101/2022.02.25.481696
Patrick M. Schaefer
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leonardo Scherer Alves
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria Lvova
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jessica Huang
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Komal Rathi
2Department of Biomedical Informatics, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Janssen
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arrienne Butic
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tal Yardeni
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryan Morrow
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie Lott
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kierstin Keller
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benjamin A. Garcia
3Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clair A. Francomano
4Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas C. Wallace
1Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, PA, 19104
5Department of Pediatrics, Division of Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wallaced1@chop.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

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.

Competing Interest Statement

Douglas 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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted February 25, 2022.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree
Patrick M. Schaefer, Leonardo Scherer Alves, Maria Lvova, Jessica Huang, Komal Rathi, Kevin Janssen, Arrienne Butic, Tal Yardeni, Ryan Morrow, Marie Lott, Kierstin Keller, Benjamin A. Garcia, Clair A. Francomano, Douglas C. Wallace
bioRxiv 2022.02.25.481696; doi: https://doi.org/10.1101/2022.02.25.481696
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree
Patrick M. Schaefer, Leonardo Scherer Alves, Maria Lvova, Jessica Huang, Komal Rathi, Kevin Janssen, Arrienne Butic, Tal Yardeni, Ryan Morrow, Marie Lott, Kierstin Keller, Benjamin A. Garcia, Clair A. Francomano, Douglas C. Wallace
bioRxiv 2022.02.25.481696; doi: https://doi.org/10.1101/2022.02.25.481696

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4234)
  • Biochemistry (9135)
  • Bioengineering (6784)
  • Bioinformatics (23999)
  • Biophysics (12129)
  • Cancer Biology (9534)
  • Cell Biology (13777)
  • Clinical Trials (138)
  • Developmental Biology (7635)
  • Ecology (11701)
  • Epidemiology (2066)
  • Evolutionary Biology (15512)
  • Genetics (10644)
  • Genomics (14325)
  • Immunology (9482)
  • Microbiology (22839)
  • Molecular Biology (9090)
  • Neuroscience (48989)
  • Paleontology (355)
  • Pathology (1482)
  • Pharmacology and Toxicology (2570)
  • Physiology (3845)
  • Plant Biology (8331)
  • Scientific Communication and Education (1471)
  • Synthetic Biology (2296)
  • Systems Biology (6190)
  • Zoology (1301)