Mitochondrial Disease Testing at CENTOGENE
What are mitochondrial diseases?
Mitochondrial diseases are genetic conditions that occur when mitochondria are failing to produce enough energy for cell. Genetic mutations in the mitochondrial genome, or nuclear genes encoding proteins functional inside mitochondria, are causing developmental, neurological, muscular and cognitive disabilities with symptoms including poor growth, loss of muscle coordination, muscle weakness and pain, seizures, vision and/or hearing loss, gastrointestinal issues, learning disabilities and organ failure.
Mitochondrial diseases are estimated to affect 1 in 4,000 people. To date, there is NO treatment and NO cure for mitochondrial diseases.
The most common types of mitochondrial myopathy are (figure 1):
- Kearns-Sayre syndrome (KSS)
- Leigh’s syndrome and maternally inherited Leigh’s syndrome (MILS)
- Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)
- Myoclonus epilepsy with ragged red fibers (MERRF)
- Neuropathy, ataxia and retinitis pigmentosa (NARP)
- Pearson syndrome
- Chronic progressive external ophthalmoplegia (CPEO)
- Myogastrointestinal encephalomyopathy (MNGIE).
What are the major symptoms of mitochondrial diseases?
Mitochondrial DNA disease commonly affects multiple different organs, with symptoms including (Figure 1):
- Loss of movement control, muscle weakness
- Neurological problems, seizures
- Developmental delay, learning disabilities
- Visual and/or hearing problems
- Heart, liver or kidney disease
- Gastrointestinal disorders
How do we inherit mitochondrial diseases?
Only the mother’s mitochondrial DNA is passed on to the next generation. Cells contain hundreds of
mitochondria, and each mitochondrion contains several copies of mitochondrial DNA. When different
mutations are present in all mitochondria in the same organism, this state is called “homoplasmy” and when only a proportion of mitochondria are carrying mutations or genetic changes it is recognized as
“heteroplasmy”. At CENTOGENE we have complex new techniques able to identify levels of heteroplasmy in the patients affected with mitochondrial diseases.
Rarely mitochondrial disease is inherited in an X-linked or autosomal dominant pattern. A combination of chromosomal and mitochondrial errors has also been reported to cause mitochondrial myopathy, in
particular myogastrointestinal encephalomyopathy (MNGIE).
What causes mitochondrial diseases?
- Mutations of nuclear genes, localized in the nucleus of the cell can cause recessive or dominantly
inherited mitochondrial diseases.
- Mutations in mitochondrial DNA (mtDNA).
- Mutations in both nuclear genes and mtDNA.
- Sporadic mutations, mostly deletions of large parts of the mitochondrial DNA.
- Toxic substances or some drugs can trigger mitochondrial disease.
Why do we need genetic testing for mitochondrial diseases?
Mitochondrial diseases are difficult to diagnose and they can present symptoms long after birth. To improve quality of life for adults and children affected by mitochondrial disease we need to establish diagnosis as soon as possible and this is possible only using genetic testing.
What tests for diagnostics of mitochondrial diseases are offered by CENTOGENE?
CENTOGENE has designed special panel for diagnostics of mitochondrial diseases.
CentoMito™ Comprehensive that includes genes:
AARS2; AASS; ABAT; ABCB6; ABCB7; ABCD1; ABCD3; ACACA; ACAD8; ACAD9; ACADM; ACADS; ACADSB; ACADVL; ACAT1; ACO2; ACOX1; ACSF3; ACSL4; ADCK3; ADCK4; AFG3L2; AGK; AGXT; AIFM1; AK2; ALAS2; ALDH18A1; ALDH2; ALDH3A2; ALDH4A1; ALDH5A1; ALDH6A1; ALDH7A1; AMACR; AMT; APOPT1; ATIC; ATP5A1; ATP5E; ATP7B; ATPAF2; ATXN2; AUH; BAX; BCKDHA;
BCKDHB; BCKDK; BCL2; BCS1L; BOLA3; BRIP1; BTD; C10orf2; C12orf65; CA5A; CASP8; CAT; CHCHD10; CISD2; CLPB; CLPP; COA5; COA6; COASY; COMT; COQ2; COQ4; COQ6; COQ9; COX10; COX14; COX15; COX20; COX4I2; COX6A1; COX6B1; COX7B; CPOX; CPS1; CPT1A; CPT1C; CPT2; CRBN; CYB5A; CYB5R3; CYC1; CYCS; CYP11A1; CYP11B1; CYP11B2; CYP24A1; CYP27A1; CYP27B1; D2HGDH; DARS2; DBT; DECR1; DGUOK; DHCR24; DHODH; DHTKD1; DIABLO; DLAT; DLD; DMGDH; DMPK; DNA2; DNAJC19; DNM1L; EARS2; ECHS1; EHHADH; ELAC2; EPHX2; ETFA; ETFB; ETFDH; ETHE1; FARS2; FASTKD2; FBXL4; FECH; FH; FKBP10; FOXRED1; FTH1; FXN; GARS; GATM; GCDH; GCSH; GDAP1; GFER; GFM1; GFM2; GK; GLDC; GLRX5; GLUD1; GLYCTK; GPI; GPT2; GPX1; GRHPR; GSR; GTPBP3; HADH; HADHA; HADHB; HARS2; HAX1; HCCS; HIBCH; HINT1; HK1; HLCS; HMBS; HMGCL; HMGCS2; HOGA1; HSD17B10; HSD17B4; HSD3B2; HSPA9; HSPD1; HTRA2; IARS2; IBA57; IDH2; IDH3B; ISCA2; ISCU; IVD; KARS; KIF1B; KRT5; L2HGDH; LARS2; LIAS; LIPT1; LONP1; LRPPRC; LYRM4; LYRM7; MAOA; MAOB; MARS2; MCCC1; MCCC2; MCEE; MFN2; MGME1; MICU1; MIP; MLH1; MLYCD; MMAA; MMAB; MMACHC; MMADHC; MOCS1; MPC1; MPV17; MRPL3; MRPL44; MRPS16; MRPS22; MSRB3; MTFMT; MTO1; MTPAP; MTRR; MUT; MUTYH; NADK2; NAGS; NARS2;
NDUFA1; NDUFA10; NDUFA11; NDUFA12; NDUFA2; NDUFA4; NDUFA9; NDUFAF1; NDUFAF2;
NDUFAF3; NDUFAF4; NDUFAF5; NDUFAF6; NDUFB11; NDUFB3; NDUFB9; NDUFS1; NDUFS2; NDUFS3; NDUFS4; NDUFS6; NDUFS7; NDUFS8; NDUFV1; NDUFV2; NFU1; NNT; NTHL1; NUBPL; OAT; OGDH; OGG1; OPA1; OPA3; OTC; OXCT1; P4HB; PAM16; PANK2; PARK7; PC; PCCA; PCCB; PCK2; PDHA1; PDHB; PDHX; PDK3; PDP1; PDSS1; PDSS2; PDX1; PET100; PEX11B; PHYH; PINK1; PKLR; PNPLA8; PNPO; PNPT1; POLG; POLG2; PPM1K; PPOX; PRODH; PTGS1; PTRF; PTRH2; PTS; PUS1; PYCR1; PYCR2; QDPR; RARS; RARS2; RDH11; RECQL4; RMND1; RNASEH1; RNASEL; RPIA; RPL35A; RPS14; RRM2B; SARDH; SARS2; SCO1; SCO2; SCP2; SDHA; SDHAF1; SDHAF2; SDHB; SDHC; SDHD; SECISBP2; SERAC1; SFXN4; SLC16A1; SLC19A3; SLC25A1; SLC25A12; SLC25A13; SLC25A15; SLC25A19; SLC25A20; SLC25A22; SLC25A3; SLC25A38; SLC25A4; SLC25A46; SLC37A4; SLC9A6; SNAP29; SOD1; SOD2; SPG7; SPR; SPTLC2; STAR; STOM; SUCLA2; SUCLG1; SUGCT; SUOX; SURF1; TACO1; TARS2; TCIRG1; TIMM44; TIMM8A; TK2; TMEM126A; TMEM70; TMLHE; TPI1; TPK1; TRMU; TRNT1; TSFM; TTC19; TUBB3; TUFM; TXNRD2; TYMP; UNG; UQCC2; UQCRB; UQCRC2; UQCRQ; VARS2; WDR81; XPNPEP3; YARS2 and complete mitochondrial genome.
By targeting nuclear encoded genes, as well as mitochondrial encoded genes this panel provides a
comprehensive test for patients with mitochondrial deficiency as evident from the analysis of biopsy
material or a suspicion of mitochondrial disease based on patient’s symptoms.
CentoMito™ Comprehensive covers the entire mitochondrial genome (100% coverage at >1000x) along with 372 nuclear genes related to the mitochondrial diseases (mean coverage of 120x, with >94% of bases
covered at ≥20x).
CentoMito™ Comprehensive includes sequence analysis of 372 nuclear encoded
mitochondrial proteins and complete mitochondrial genome, with detection of heteroplasmy down to 15%.
CENTOGENE is also offering CentoMito™ Genome, that includes all mitochondrial genes: MT-ND1, MT-ND2, MT-CO1, MT-CO2, MT-ATP8, MT-ATP6, MT-CO3, MT-ND3, MT-ND4L, MT-ND4, MT-ND5, MT-ND6, MT-CYB, MT-TF, MT-RNR1, MT-TV, MT-RNR2, MT-TL1, MT-TI, MT-TQ, MT-TM, MT-TW, MT-TA, MT-TN, MT-TC, MT-TY, MT-TS1, MT-TD, MT-TK, MT-TG, MT-TR, MT-TH, MT-TS2, MT-TL2, MT-TE, MT-TT, MT-TP.
- At CENTOGENE we need only 1mL EDTA blood or 2µg DNA for the analysis of either the Mitochondrial diseases panel or for CentoMito™ Comprehensive panel
- Turnaround time for both panels is < 45 days.
Who should be tested for mitochondrial diseases?
- Individuals with clinical symptoms characteristic of a specific mitochondrial disorder
- Individuals with any progressive multisystem disorder of unknown etiology
- Individuals with multiple complex neurologic features or a single neurological symptom with other
- Children presenting with lactic acidosis
- Presymptomatic testing for at-risk family members
What type of test results can you expect?
- Positive result - indicates that a previously understood disease-causing mutation was identified. This result can help the physician to assess the risk of experiencing certain symptoms and indicate the best way how to treat the disease. Positive result may also identify family members at-risk for having the
mutation and carrier testing may be recommended.
- Negative result - does not necessarily rule out a mitochondrial disorder, and the patient should be managed according to clinical symptoms. Possible reasons for a negative result could be that the
patient may have a mutation in a gene not covered by testing panel, or it could be mutation which is not detectable the performed test, or the patient does not have a mitochondrial disorder.
- Variant of unknown clinical significance (VUS) - indicates that we have identified change in the DNA, but this change is not known to be associated with a disorder. To clarify the clinical significance of the variant, testing other family members may be helpful.
How can mitochondrial diseases be treated?
There are no cures for mitochondrial diseases, but treatment can help reduce symptoms or delay or prevent the progression of the disease. Only with a diagnosis obtained by means of genetic testing we can suggest the best fitting therapy or management for the affected patients.
- Physiotherapy can help to maintain muscle function and muscle fatigue can be improved by regular
- A good diet, including adequate vitamin and supplements intake (for example creatine, L-carnitine and coenzyme Q10) and the avoidance of obesity are important.
- Problems with breathing require treatment with occasional or permanent ventilator support.
- Certain drugs may affect mitochondrial function, and it is generally recommend avoiding those drugs and alcohol.
- Diabetes can be treated insulin and drugs to treat seizures and headaches may be prescribed.
- Specialists may be required to treat vision, hearing, speech and swallowing difficulties as necessary.
Why should you use CENTOGENE for mitochondrial disease genetic testing?
- CENTOGENE is offering highly sensitive genetic testing using new technologies: next-generation
sequencing, deletion/duplication analysis by several methods, mitochondrial DNA point mutation
analysis by Sanger sequencing and qPCR and highly professional bioinformatics support
- Multiple genes can be tested at the same time, leading to more cost-effective test and faster turn around-time
- Reports with results are written by highly experienced human geneticists and genetic counselors
- CENTOGENE has over 10 years of experience in genetic testing for rare disorders
- Patient and customer-friendly human geneticists, medical experts and customer relations team are
always available to answer all your questions.