2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Multiple mitochondrial DNA deletions in patients with myopathy

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This study conducted a retrospective analysis of 195 muscle samples from patients suspected to have a primary mitochondrial disorder or mitochondrial myopathy. The aim was to investigate the trends between mitochondrial DNA (mtDNA) findings and patient phenotypes and characteristics. Multiple mtDNA deletions, which are large scale deletions of mtDNA of different sizes in a single specimen, were detected using Next Generation Sequencing (NGS). The study found that age is a major factor for mtDNA multiple deletions, with the average age of patients with multiple deletions significantly higher than those without. The most common breakpoints for mtDNA multiple deletions were found in the m.3000_m.16,000 range, which is consistent with previously reported single large deletion breakpoints. The study also found that high depth coverage of single NGS assays can detect deletions at very low heteroplasmy levels. However, the detection limit of droplet digital PCR (ddPCR) for mtDNA large deletion heteroplasmy may not accurately quantify levels below 10%. The study showed that single heterozygous pathogenic variants in the POLG gene associated with dominant conditions can result in mtDNA multiple deletions and depletion, while single pathogenic variants associated with recessive conditions may not cause multiple deletions. It was noted that the etiology of multiple deletion cases in the majority of patients remains unknown. Overall, this study provides insights into the characteristics and trends of multiple mtDNA deletions in patients with myopathy.

Asset Subtitle

Presenting Author - Jing Wang, MD; Co-Author - Ada Chan; Co-Author - James Peterson, MS; Co-Author - Kathleen H. Wood, PhD; Co-Author - Maria Alejandra Diaz-Miranda, PhD; Co-Author - Archana Tara, PhD; Co-Author - Amy Goldstein, MD; Co-Author - Zarazuela Zolkipli-Cunningham, MD; Co-Author - Elizabeth M. McCormick, MS, LCGC; Co-Author - Colleen Muraresku, MS, LCGC; Co-Author - Matthew C. Dulik, PhD; Co-Author - Douglas Wallace, PhD; Co-Author - Marni J. Falk, MD;

Meta Tag

Genetic Testing

Mitochondria

Musculoskeletal system

Co-Author Ada Chan

Co-Author James Peterson, MS

Co-Author Kathleen H. Wood, PhD

Co-Author Maria Alejandra Diaz-Miranda, PhD

Co-Author Archana Tara, PhD

Co-Author Amy Goldstein, MD

Co-Author Zarazuela Zolkipli-Cunningham, MD

Co-Author Elizabeth M. McCormick, MS, LCGC

Co-Author Colleen Muraresku, MS, LCGC

Co-Author Matthew C. Dulik, PhD

Co-Author Douglas Wallace, PhD

Co-Author Marni J. Falk, MD

Presenting Author Jing Wang, MD

Keywords

retrospective analysis

mitochondrial disorder

mitochondrial myopathy

mtDNA findings

mtDNA deletions

Next Generation Sequencing

age factor

large deletion breakpoints

depth coverage

POLG gene