Setting a new standard for high-quality panel-based testing with mitochondrial DNA analysis

February 24, 2020

Blueprint Genetics, a Quest Diagnostics company, is introducing full mitochondrial genome analysis to its diagnostic panels in order to bring maximized diagnostic potential across medical specialties, especially in cardiology, metabolic diseases, neurology, ophthalmology, and hearing loss.

Blueprint Genetics’ mitochondrial genome DNA (mtDNA) analysis is a highly sensitive and validated assay based on hybridization-based capture of mtDNA and next-generation sequencing (NGS). The technology detects low heteroplasmy levels of mtDNA SNVs, INDELs and deletions. After a successful analytic validation, over 7,000 cases were tested for mtDNA mutations to establish the clinical utility of the assay to diagnose mitochondrial disease.

“We set out to create the largest and most comprehensive analytic and clinical validation study for mtDNA variant detection to date. End-to-end validation was complemented using a bioinformatic approach that demonstrated the successful detection of thousands of simulated mtDNA mutations at very low heteroplasmy levels. More transparency about successes, challenges, and limitations is needed in this field, as no gold standard has yet been established in regard to a reference assay, sample set, feasibility, and available validation studies,” said Juha Koskenvuo, Executive Director, Lab and Medical at Blueprint Genetics.

Blueprint Genetics’ mtDNA testing includes sequencing and copy number variant analysis of the entire mitochondrial genome (37 genes) which can be ordered alone or added to any panel. It has also been added to 30 existing panels where mitochondrial DNA testing is expected to have an impact on the diagnostic potential.

“Combining diagnostic panels that focus on nuclear-encoded genes with mitochondrial DNA analysis is a powerful strategy to further boost the diagnostic yield of panel testing. Our test development, extensive analytical validations and rapidly accumulating clinical experience with tens of thousands of rare disease patients are a great opportunity for building know-how and expertise that will help us to provide even better test results for health care providers and their patients,” Koskenvuo continued.

Symptoms of mtDNA disorders range from fatigue and exercise intolerance to hearing loss, seizures, strokes, heart failure, diabetes, and kidney failure. They can be multisystemic or limited to a single organ and vary greatly even between family members. The addition of mitochondrial DNA testing improves Blueprint Genetics’ diagnostic capabilities providing a greater diagnostic potential for individuals suspected to have an inherited disease.

In short:

  • A new Mitochondrial Genome Test is now available, including sequencing of the entire mitochondrial genome and copy number variant (CNV) analysis
  • Over 30 panels have been updated to include mitochondrial genome sequencing and CNV analysis
  • Mean read depth for the mitochondrial genome is 18,224x with 100% of base pairs covered with at least 1,000x
  • Sensitivity to detect SNVs at 5% heteroplasmy is 92.3%
  • Sensitivity to detect Indels at 5% heteroplasmy is >94%
  • Sensitivity to detect large 500bp – 5,000kb deletions at 10% heteroplasmy is 99%

Read more:

Further information

Juha Koskenvuo, Executive Director, Lab and Medical,
Juulia Simonen, Communication Manager, tel. +358 50 305 9018,

About Blueprint Genetics

Blueprint Genetics is a leading specialty genetics and bioinformatics company focused on rare inherited diseases. The company is based in Helsinki with a US hub in Seattle, and a customer base spanning over 70 countries.


Subscribe to our press releases