Comprehensive Mitochondrial Genome Analysis

Comprehensive Mitochondrial Genome Analysis

  • Mitochondria play a critical role in essential cellular functions including energy generation and many cellular pathways. Mutations of the mitochondrial genome (mtDNA) can lead to mitochondrial dysfunction and cause disorders.
  • Mitochondrial disorders are clinically heterogeneous with variability of clinical presentation, age of onset, course of disease and genetic etiologies. Some mitochondrial disorders only affect a single organ, but most involve multiple organ systems, particularly, those where the cells have high energy demands, such as brain, skeletal muscles, heart, eyes and the endocrine system. Clinical features of mitochondrial disease include developmental delay, seizures, sensorineural deafness, optic atrophy, pigmentary retinopathy, ptosis, external ophthalmoplegia, myopathy, exercise intolerance, cardiomyopathy, diabetes mellitus, stroke-like episodes and others. Some conditions are mainly caused by mtDNA deletion such as Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), and Pearson syndrome. Others are more likely associated with single nucleotide changes, such as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). Mitochondrial disorders can be caused by mutation in mtDNA or nuclear DNA (nDNA).
  • Mitochondrial disorders caused by mutations in mtDNA are estimated to be as frequent as 1/5000. When a mutation is located in mtDNA, the condition is maternally inherited. When mutant and wild-type mtDNA co-exist (heteroplasmy), it is very important to determine the percentage of the mutant mtDNA since the severity of disease is related with the level of heteroplasmy.
  • Genetic testing can be very helpful to make a diagnosis. This genetic testing process involves the analysis of the entire mitochondrial genome which encodes 13 proteins, 22 tRNAs and 2 ribosomal RNAs.
  • Genes (37): MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY, MT-RNR1, and MT-RNR2
    Test Code: 8100
    Clinical Indication:
    • Patient with clinical symptoms or pathology study suspected of a mitochondrial disorder
    • Molecular confirmation of a clinical diagnosis
    Test Info Sheet: Comprehensive Mitochondrial Genome Analysis
  • Requisition: Mitochondrial Test Requisition Form
  • Turn-Around Time: 2-4 Weeks
  • Preferred Specimen: 3-5 mL Whole Blood – Lavender Top Tube
  • Other Specimens: See details here
  • CPT Codes: 81460, 81465
    Pricing:
     Please contact us at (949) 916-8886 or inquiries@apollogen.com
  • Methodology: Long-range PCR followed by Next-Generation Sequencing (NGS)
  • Related Tests:
    Mitochondrial DNA Deletion Analysis
    Mitochondrial Nuclear Gene Panel
    Mitochondrial Depletion Syndrome Panel
  • References:
  • 1. Taylor, R. W. & Turnbull, D. M. Mitochondrial DNA mutations in human disease. Nat. Rev. Genet. 6, 389–402 (2005).
    2. Leonard, J. V. & Schapira, A. H. Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet Lond. Engl. 355, 299–304 (2000).
    3. Scaglia, F. et al. Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease. Pediatrics 114, 925–931 (2004).
    4. Chinnery, P. F. in GeneReviews(R) (eds. Pagon, R. A. et al.) (University of Washington, Seattle, 2014).
    5. Wallace, D. C. & Chalkia, D. Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease. Cold Spring Harb. Perspect. Biol. 5, a021220 (2013).
    6. Arpa, J. et al. Prevalence and progression of mitochondrial diseases: a study of 50 patients. Muscle Nerve 28, 690–695 (2003).
    7. Schaefer, A. M. et al. Prevalence of mitochondrial DNA disease in adults. Ann. Neurol. 63, 35–39 (2008).
    8. Tang, S. & Huang, T. Characterization of mitochondrial DNA heteroplasmy using a parallel sequencing system. Biotechniques 48, 287–296 (2010).
    9. Huang, T. Next generation sequencing to characterize mitochondrial genomic DNA heteroplasmy. Curr Protoc Hum Genet Chapter 19, Unit19.8 (2011).
    10. Kang, E. et al. Age-related accumulation of somatic mitochondrial DNA mutations in adult-derived human iPSCs. Cell Stem Cell 18, 625-636 (2016).
    11. http://www.mitomap.org/MITOMAP
    12. Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. Off. J. Am. Coll. Med. Genet. 17, 405–424 (2015).
    13. http://www.umdf.org/

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