Mitochondrial Genetics in Health and Disease

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 15 January 2027 | Viewed by 598

Editor


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Guest Editor
Children's Hospital of Philadelphia, Philadelphia, PA, USA
Interests: comprehensive analysis of mitochondrial DNA; clinical application of genome sequencing analysis for neurodevelopmental disorders, epilepsy, and mitochondrial disorders

Special Issue Information

Dear Colleagues,

We would like to invite you to contribute to this Special Issue of the journal Genes, entitled “Mitochondrial Genetics in Health and Disease”.

Mitochondria, the powerhouses of cells, play a pivotal role in cellular metabolism, signaling, and maintaining homeostasis. Mitochondrial dysfunction has been implicated in various chronic conditions, including neurodegenerative diseases, metabolic disorders, and heart and liver diseases. Advancements in mitochondrial genetics have significantly expanded our understanding of both inherited and acquired diseases. This Special Issue aims to bring together high-quality original research articles that explore recent discoveries, methodological innovations, and emerging concepts in mitochondrial genetics and genomics. These concepts have the potential to revolutionize our understanding of human health and disease. We particularly welcome contributions that address, but are not limited to, advancements in mitochondrial DNA analysis, diagnostic and therapeutic approaches targeting mitochondrial dysfunction, model systems, and novel technologies for studying primary mitochondrial disorders.

Given your expertise and contributions to this field, we believe your work would be a valuable addition to this Special Issue and of significant interest to the journal’s readership.

Dr. Jing Wang
Guest Editor

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Keywords

  • primary mitochondrial disorders
  • mitochondrial DNA
  • mitochondrial dysfunction
  • diagnosis
  • therapeutic approaches

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Published Papers (1 paper)

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Research

19 pages, 14726 KB  
Article
MSeqDR PMD-VR: An Expert-Curated Virtual Registry of 11,000 Mitochondrial Disease Cases Established Through Literature Mining and Generative AI Augmentation
by Lishuang Shen, Marie T. Lott, Elizabeth M. Mccormick, Colleen C. Muraresku, Kierstin Keller, Douglas C. Wallace, Zarazuela Zolkipli-Cunningham, Shamima Rahman, Marni J. Falk and Xiaowu Gai
Genes 2026, 17(7), 757; https://doi.org/10.3390/genes17070757 - 30 Jun 2026
Viewed by 222
Abstract
Background/Objectives: Patient registries are essential for rare disease research, yet the extensive genetic and phenotypic heterogeneity of primary mitochondrial diseases (PMDs) makes traditional registry development slow and resource-intensive. We established the MSeqDR PMD virtual registry (PMD-VR) to address this gap through systematic literature [...] Read more.
Background/Objectives: Patient registries are essential for rare disease research, yet the extensive genetic and phenotypic heterogeneity of primary mitochondrial diseases (PMDs) makes traditional registry development slow and resource-intensive. We established the MSeqDR PMD virtual registry (PMD-VR) to address this gap through systematic literature mining and semi-automated data harmonization. Methods: The PMD-VR captures, standardizes, and harmonizes published case-level PMD data using a semi-automated curation pipeline. A data transformation framework maps heterogeneous raw data terms to standardized common data elements (CDEs). A generative AI (GenAI) platform leveraging large language models (LLMs), augmented by Human Phenotype Ontology (HPO) and external biomedical knowledge sources, accelerates data transformation and generates simulated clinical reports. Results: Currently, PMD-VR contains approximately 11,000 de-identified literature-derived cases, including over 2300 Leigh syndrome spectrum (LSS), 278 MELAS, and 300 CPEO cases. The pipeline mapped 872 heterogeneous terms to 102 standardized CDEs. Pathogenicity assessments were captured for variants in over 7900 cases, including 3800 with mtDNA pathogenic or likely pathogenic variants. Modes of inheritance were inferred for 5212 cases. PMD-VR has supported ClinGen Mitochondrial Diseases Gene Curation Expert Panel (Mito-GCEP) efforts, providing phenotyped evidence for 440 curated LSS cases across 113 PMD genes. Conclusions: PMD-VR is among the largest single PMD registries, offering a scalable, web-accessible platform for generating analysis-ready cohorts from the published literature. It represents a rich resource enabling comprehensive PMD characterization with unprecedented breadth of genetic and phenotypic knowledge. Full article
(This article belongs to the Special Issue Mitochondrial Genetics in Health and Disease)
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