Mitochondrial Nuclear Gene Panel

Mitochondrial Nuclear Gene Panel

  • Mitochondrial diseases are genetically heterogeneous and they can be caused by pathogenic variants in mitochondrial DNA (mtDNA) and/or nuclear DNA. The majority of mitochondrial proteins are encoded in the nuclear genome and transported into the mitochondria. Therefore, in some cases, to achieve a high diagnostic yield, testing of both nuclear genes associated with mitochondrial diseases and mtDNA is recommended. Mitochondrial disorders can be inherited maternally, or in an autosomal dominant, recessive or X-linked manner if nuclear genes are involved.
  • The prevalence of mitochondrial disorders is higher than previously thought and is conservatively estimated to be 1/8500 – 1/5000 according to the most recent studies. Mitochondrial disorders are clinically heterogeneous, in terms of specific clinical presentation, age of onset, course of disease and genetic cause. 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 symptoms may present at any age and are highly variable and non-specific.
  • Individuals affected with a discrete mitochondrial disorder, including Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), 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), can exhibit extremely variable clinical presentation and overlapping features of other mitochondrial syndromes. Common features of mitochondrial disease may include ptosis, external ophthalmoplegia, proximal myopathy, exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, diabetes mellitus, encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, spasticity, chorea and dementia.
  • Genes (503):

AAAS, AARS2, AASS, ABAT, ABCB6, ABCB7, ABCC8, ABCC9, ABCD1, ABCD3, ACACA, ACACB, ACAD8, ACAD9, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACAT2, ACHE, ACLY, ACO2, ACSF3, ACSL4, ACSL5, ACSM3, ADSL, AFG3L2, AGK, AGPS, AGXT, AGXT2, AIFM1, AK2, AKAP10, AKR7A2, AKT1, AKT2, ALAS2, ALDH18A1, ALDH2, ALDH3A2, ALDH4A1, ALDH5A1, ALDH6A1, ALDH7A1, AMACR, AMT, ANK2, ANKRD26, APTX, ARMS2, AS3MT, ASS1, ATIC, ATP10D, ATP5E, ATP5SL, ATP7B, ATP8B1, ATPAF2, ATXN7, AUH, BAX, BCAT1, BCAT2, BCKDHA, BCKDHB, BCL2, BCS1L, BOLA3, C10ORF2, C12ORF65, CACNA1A, CACNA1S, CACNA2D1, CASP8, CDC42BPB, CDKL5, CFTR, CHAT, CHDH, CHRNA4, CHRNB2, CISD2, CKM, CLCN1, CLCN2, CLCN5, CLCN7, CLCNKB, CLN3, CLN5, CLN6, CLN8, CLYBL, CNR1, COA5, COMT, COQ2, COQ4, COQ5, COQ6, COQ9, COX10, COX14, COX15, COX4I1, COX4I2, COX6B1, COX7A2, CPOX, CPS1, CPT1A, CPT1B, CPT2, CTSD, CYB5A, CYB5R3, CYBA, CYBB, CYCS, CYP11A1, CYP11B1, CYP11B2, CYP24A1, CYP27A1, CYP27B1, D2HGDH, DARS2, DBT, DDAH1, DDC, DECR1, DGUOK, DHODH, DIABLO, DISC1, DLAT, DLD, DMGDH, DMPK, DNAJC19, DNAJC5, DNM1L, DTNBP1, EARS2, ECI1, ECSIT, ELAC2, ELN, ENO1, ENO3, ETFA, ETFB, ETFDH, ETHE1, FAAH, FARS2, FASN, FASTKD2, FBP1, FECH, FH, FOLR1, FOXC1, FOXG1, FOXRED1, FPGS, FTH1, FXN, G6PC, G6PD, GAD1, GAD2, GALC, GARS, GATM, GCDH, GCK, GCSH, GDAP1, GFER, GFM1, GK, GLDC, GLO1, GLRA1, GLRX5, GLS, GLUD1, GLYCTK, GNAS, GNPAT, GPAM, GPD1, GPD2, GPI, GPX1, GPX4, GYS1, GYS2, H6PD, HADH, HADHA, HADHB, HARS, HARS2, HCCS, HIBCH, HIGD2A, HK1, HK2, HLCS, HMGCL, HMGCS2, HOGA1, HSD17B10, HSD17B4, HSD3B1, HSD3B2, HSPA9, HSPB7, HSPD1, HTRA2, HTT, IDE, IDH1, IDH2, IDH3B, IMMP2L, IMMT, INSR, ISCU, IVD, KARS, KCNA1, KCNE1, KCNE2, KCNH2, KCNJ11, KCNJ2, KCNQ1, KCNQ2, KCNQ3, KIF1B, KRT5, KYNU, L2HGDH, LARS2, LDHA, LDHB, LETM1, LIAS, LRPPRC, LRRK2, MAOA, MAOB, MARS2, MAVS, MCCC1, MCCC2, MCEE, MDH1, MECP2, MED23, MEN1, MFN2, MFSD8, MGLL, MGST3, MLYCD, MMAA, MMAB, MMACHC, MMADHC, MOCOS, MOCS1, MOCS2, MOGS, MPV17, MRPL3, MRPL48, MRPS16, MRPS22, MRRF, MTCH2, MTFMT, MTHFD1, MTHFD1L, MTHFS, MTO1, MTPAP, MTRR, MUT, MUTYH, NAGS, NARS2, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA13, NDUFA2, NDUFA4, NDUFA6, NDUFA7, NDUFA8, NDUFA9, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFB1, NDUFB3, NDUFB6, NDUFB9, NDUFC2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS5, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NDUFV3, NFU1, NIPSNAP1, NIPSNAP3A, NLRX1, NME1, NOS3, NPL, NRXN1, NTHL1, NUBPL, OAT, OGG1, OPA1, OPA3, OTC, OXCT1, PACRG, PAH, PAK7, PANK2, PARK2, PARL, PARP1, PC, PCCA, PCCB, PCK1, PCK2, PDHA1, PDHB, PDHX, PDP1, PDSS1, PDSS2, PDX1, PEX1, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, PGAM2, PGK1, PHB, PHYH, PKLR, PMPCA, PNKD, PNMT, POLG, POLG2, POLRMT, PPARGC1A, PPARGC1B, PPOX, PPT1, PREPL, PRODH, PTGES2, PTS, PUS1, PYCR1, QDPR, RAB11FIP5, RARS2, REEP1, RNASEL, RPL35A, RRM2B, RSPH9, RYR1, RYR2, SACS, SARDH, SARS2, SCN1A, SCN1B, SCN2A, SCN4A, SCN5A, SCO1, SCO2, SCP2, SDHA, SDHAF1, SDHAF2, SDHB, SDHC, SDHD, SECISBP2, SHMT1, SIRT1, SIRT3, SIRT5, SLC16A1, SLC19A2, SLC22A4, SLC22A5, SLC25A12, SLC25A13, SLC25A15, SLC25A19, SLC25A20, SLC25A22, SLC25A3, SLC25A38, SLC25A39, SLC25A4, SLC27A4, SLC2A1, SLC3A1, SPAST, SPG20, SPG7, SPR, SPTLC2, STAR, SUCLA2, SUCLG1, SUOX, SURF1, TACO1, TAP1, TAT, TAZ, TCIRG1, TDP1, TFAM, TFB1M, TIMM44, TIMM8A, TK2, TMEM126A, TMEM70, TOMM40, TOP1MT, TP53, TPH2, TPI1, TPP1, TRMU, TSFM, TSPO, TST, TTC19, TUFM, TXN2, TXNRD2, TYMP, UBE3A, UCP1, UCP2, UCP3, UNG, UQCRB, UQCRQ, UROS, USP24, WFS1, WWOX, XPNPEP3, and YARS2

  • Test Code: 8300
    Clinical Indications:
    • Patient with clinical symptoms or pathology study suspected of a mitochondrial disorder
    • Molecular confirmation of a clinical diagnosis
    Test Info Sheet: Mitochondrial Nuclear Gene Panel
    Requisition: Mitochondrial Test Requisition Form
  • Turn-Around Time: 4 Weeks
    Preferred Specimen: 3-5 mL Whole Blood – Lavender Top Tube
    Other Specimens: See details here
  • CPT Codes: 81440
    Pricing: Please contact us at (949) 916-8886 or inquiries@apollogen.com
  • Methodology: Next-Generation Sequencing (NGS)
    Related Tests:
    Mitochondrial Depletion Syndrome Panel
    Comprehensive Mitochondrial Genome Analysis
    Mitochondrial DNA Deletion Analysis
  • 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. Gorman, G. S. et al. Mitochondrial diseases. Nat. Rev. Dis. Primer 2, 16080 (2016).
    6. Gorman, G. S. et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann. Neurol. 77, 753–759 (2015).
    7. Arpa, J. et al. Prevalence and progression of mitochondrial diseases: a study of 50 patients. Muscle Nerve 28, 690–695 (2003).
    8. Schaefer, A. M. et al. Prevalence of mitochondrial DNA disease in adults. Ann. Neurol. 63, 35–39 (2008).
    9. 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).
    10. http://www.umdf.org/
    11. http://www.mitomap.org/MITOMAP

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