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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessMyopathy, mitochondrial, incl. CPEO; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Myopathy (mitochondrial + CPEO) comprising 25 guideline-curated genes and altogether 130 curated genes

ID
MP9345
Number of genes
101 Accredited laboratory test
Examined sequence length
37,5 kb (Core-/Core-canditate-Genes)
135,1 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
  • Gewebeprobe
Diagnostic indications

NGS +

[[Sanger]]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
AFG3L22394NM_006796.3AD, AR
AGK1269NM_018238.4AR
CHCHD10429NM_213720.3AR
COX20357NM_198076.6AR
DGUOK834NM_080916.3AR
DNA23183NM_001080449.3AD
FBXL41866NM_012160.5AR
GFER618NM_005262.3AR
IBA571071NM_001010867.4AR
ISCU504NM_213595.4AR
MGME11035NM_052865.4AR
NDUFS12184NM_005006.7AR
OPA12883NM_015560.3AD, AR
POLG3720NM_002693.3AR
POLG21458NM_007215.4AD, AR
PUS11284NM_025215.6AR
RNASEH1869NM_002936.6AR
RRM2B1272NM_015713.5AR
SDHA1995NM_004168.4AR
SLC25A4897NM_001151.4AD
SPG72388NM_003119.4AR, AD
TWNK2055NM_021830.5AR, AD
TYMP1449NM_001953.5AR
YARS21434NM_001040436.3AR
ABAT1503NM_000663.5AR
ABHD51050NM_016006.6AR
ACAD91866NM_014049.5AR
BCS1L1260NM_004328.5AR
CASQ11191NM_001231.5AD
COA6378NM_001012985.2AR
COQ21266NM_015697.9AR
COQ4798NM_016035.5AR
COQ8A1944NM_020247.5AR
COQ9957NM_020312.4AR
COX101332NM_001303.4AR
COX151167NM_004376.7AR
CPT21977NM_000098.3AR
DNM22613NM_001005360.3AD
EARS21572NM_001083614.2AR
ECHS1873NM_004092.4AR
ETHE1765NM_014297.5AR
FARS21356NM_006567.5AR
FDX2566NM_001031734.4AR
FLAD12021NM_001184891.2AR
FOXRED11461NM_017547.4AR
GFM12256NM_024996.7AR
IARS23039NM_018060.4AR
LIPT11122NM_001204830.2AR
LRPPRC4185NM_133259.4AR
MFN22274NM_014874.4AR
MICU11437NM_006077.4AR
MPV17531NM_002437.5AR
MSTO11953NM_001256532.1AD, AR
MTFMT1170NM_139242.4AR
NDUFA1213NM_004541.4XL
NDUFA101068NM_004544.4AR
NDUFA2300NM_002488.5AR
NDUFA4246NM_002489.4AR
NDUFA91134NM_005002.5AR
NDUFAF2510NM_174889.5AR
NDUFAF5954NM_001039375.3AR
NDUFAF61002NM_152416.4AR
NDUFS21374NM_004550.5AR
NDUFS3795NM_004551.3AR
NDUFS4528NM_002495.4AR
NDUFS7642NM_024407.5AR
NDUFS8633NM_002496.4AR
NDUFV11368NM_007103.4AR
PDHA11173NM_000284.4XL
PDHB1080NM_000925.4AR
PDHX1506NM_003477.3AR
PDSS21200NM_020381.4AR
PET100222NM_001171155.2AR
PNPLA21515NM_020376.4AR
PNPLA82358NM_001256007.3AR
PNPT12352NM_033109.5AR
QRSL11744NM_018292.5AR
SCO1906NM_004589.4AR
SCO2801NM_005138.3AR
SDHAF1348NM_001042631.3AR
SDHB843NM_003000.3AR
SDHC510NM_003001.5AD
SDHD480NM_003002.4AR
SERAC11965NM_032861.4AR
SLC19A31491NM_025243.4AR
SLC25A31086NM_002635.4AR
SLC52A11347NM_001104577.2AD
SLC52A21338NM_024531.5AR
SLC52A31410NM_033409.4AR
SUCLA21392NM_003850.3AR
SUCLG11041NM_003849.4AR
SURF1903NM_003172.4AR
TACO1894NM_016360.4AR, Mi
TAFAZZIN879NM_000116.5XLR
TK2705NM_001172643.1AR
TOP3A3006NM_004618.5AR
TPK1585NM_001042482.2AR
TRMU1266NM_018006.5AR
TSFM1041NM_001172696.2AR
TTC19822NM_001271420.2AR
VARS22772NM_001167733.3AR

Informations about the disease

Clinical Comment

Mitochondrial myopathies are a group of progressive muscle diseases caused primarily by impairment of oxidative phosphorylation. Myopathy is one of the most common manifestations of mitochondrial diseases in adults due to the high cellular energy demand of skeletal muscle. However, patients with mitochondrial myopathy often also show dysfunction in multiple organ systems, leading to wide variability in clinical phenotype and prognosis. Thus these disorders are virtually always multisystemic disorders, presenting with a variety of neurologic, hepatic and gastrointestinal symptoms, among others. Myopathy often results in exercise intolerance, cramping, and fatigue. Proximal myopathy is the most common form; the degree of weakness is variable, and patients are often rapidly fatigued. In some patients, the progressive muscle weakness may require mechanical ventilation. Chronic progressive external ophthalmoplegia is a common presentation in patients with mitochondrial disease and is often associated with proximal myopathy. In addition, exercise-induced muscle pain is common, rarely rhabdomyolysis, while fatigue is the symptom most commonly reported by patients. Based on a virtually immense number of nuclear genome mutations, the diseases from this group are mostly inherited in an autosomal recessive manner, less frequently in an autosomal dominant manner and only exceptionally in an X-linked manner. The molecular genetic yield is very difficult to detect in mitochondrial disorders, with considerable limitations. A negative molecular genetic result does not constitute exclusion of the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1224/

 

Synonyms
  • Alias: Combined oxidative phosphorylation deficiency
  • Alias: Complex multisystem presentation
  • Alias: Disorders of mitochondrial DNA maintenance and integrity
  • Alias: Disorders of mitochondrial apoptosis
  • Alias: Disorders of mitochondrial lipid metabolism
  • Alias: Disorders of ubiquinone metabolism and biosynthesis
  • Alias: Mitochondrial disorders
  • Alias: Mitochondrial myopathy
  • Alias: Multiple respiratory chain complex deficiencies
  • Allelic: CPT II deficiency, lethal neonatal (CPT2)
  • Allelic: Charcot-Marie-Tooth disease, axonal type 2M (DNM2)
  • Allelic: Charcot-Marie-Tooth disease, dominant intermediate B (DNM2)
  • Allelic: Charcot-Marie-Tooth disease, type 4K (SURF1)
  • Allelic: Deafness, AR 70 (PNPT1)
  • Allelic: Encephalopathy, acute, infection-induced, 4, susceptibility to (CPT2)
  • Allelic: Fanconi renotubular syndrome 5 (NDUFAF6)
  • Allelic: Fazio-Londe disease (SLC52A3)
  • Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 2 (CHCHD10)
  • Allelic: Gastrointestinal stromal tumor (SDHB, SDHC)
  • Allelic: Hyperinsulinemic hypoglycemia, familial, 4 (HADH)
  • Allelic: Microcephaly, growth restriction + increased sister chromatid exchange 2 (TOP3A)
  • Allelic: Myopia 6 (SCO2)
  • Allelic: Perrault syndrome 5 (TWNK)
  • Allelic: Pheochromocytoma (SDHB, SDHD)
  • Allelic: Spastic paraplegia 77, AR (FARS2)
  • 3-hydroxyacyl-CoA dehydrogenase deficiency (HADH)
  • 3-methylglutaconic aciduria with deafness, encephalopathy + Leigh-like syndrome (SERAC1)
  • Allelic: Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17)
  • Barth syndrome (TAFFAZIN)
  • Bjornstad syndrome, GRACILE syndrome (BCS1L)
  • Brown-Vialetto-Van Laere syndrome 1 (SLC52A3)
  • Brown-Vialetto-Van Laere syndrome 2 (SLC52A2)
  • CPT II deficiency, infantile (CPT2)
  • CPT II deficiency, myopathic, stress-induced (CPT2)
  • CPT deficiency, hepatic, type IA (CPT1A)
  • Centronuclear myopathy 1 (DNM2)
  • Chanarin-Dorfman syndrome (ABHD5)
  • Charcot-Marie-Tooth disease, axonal, type 2A2A (MFN2)
  • Charcot-Marie-Tooth disease, axonal, type 2A2B (MFN2)
  • Coenzyme Q10 deficiency, primary, 1 (COQ2)
  • Coenzyme Q10 deficiency, primary, 2 (PDSS1)
  • Coenzyme Q10 deficiency, primary, 3 (PDSS2)
  • Coenzyme Q10 deficiency, primary, 4 (COQ8A)
  • Coenzyme Q10 deficiency, primary, 5 (COQ9)
  • Coenzyme Q10 deficiency, primary, 6 (COQ6)
  • Coenzyme Q10 deficiency, primary, 7 (COQ4)
  • Coenzyme Q10 deficiency, primary, 8 (COQ7)
  • Coenzyme Q10 deficiency, primary, 9 (COQ5)
  • Combined oxidative phosphorylation deficiency 1 (GFM1)
  • Combined oxidative phosphorylation deficiency 12 (EARS2)
  • Combined oxidative phosphorylation deficiency 13 (PNPT1)
  • Combined oxidative phosphorylation deficiency 14 (FARS2)
  • Combined oxidative phosphorylation deficiency 15 (MTFMT)
  • Combined oxidative phosphorylation deficiency 20 (VARS2)
  • Combined oxidative phosphorylation deficiency 3 (TSFM)
  • Combined oxidative phosphorylation deficiency 40 (QRSL1)
  • Combined oxidative phosphorylation deficiency 44 (FASTKD2)
  • Ethylmalonic encephalopathy (ETHE1)
  • Exocrine pancreatic insufficiency, dyserythropoietic anemia + calvarial hyperostosis (COX4I2)
  • GABA-transaminase deficiency (ABAT)
  • Glutaric acidemia IIC (ETFDH)
  • Hereditary motor and sensory neuropathy VIA (MFN2)
  • Lacticacidemia due to PDX1 deficiency (PDHX)
  • Leigh syndrome (BCS1L, SDHA)
  • Lethal congenital contracture syndrome 5 (DNM2)
  • Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency (FLAD1)
  • Lipoyltransferase 1 deficiency (IARS2)
  • Lipoyltransferase 1 deficiency (LIPT1)
  • Liver failure, transient infantile (TRMU)
  • Metabolic crises, recurrent, variable encephalomyopathic features, neurologic regression (SLC25A42)
  • Mitochondrial DNA depletion syndrome (AGK)
  • Mitochondrial DNA depletion syndrome 1, MNGIE type (TYMP)
  • Mitochondrial DNA depletion syndrome 11 (MGME1)
  • Mitochondrial DNA depletion syndrome 13, encephalomyopathic type (FBXL4)
  • Mitochondrial DNA depletion syndrome 16, hepatic type (POLG2)
  • Mitochondrial DNA depletion syndrome 2, myopathic type (TK2)
  • Mitochondrial DNA depletion syndrome 3, hepatocerebral type (DGUOK)
  • Mitochondrial DNA depletion syndrome 4A, Alpers type (POLG)
  • Mitochondrial DNA depletion syndrome 4B, MNGIE type (POLG)
  • Mitochondrial DNA depletion syndrome 5, encephalomyopathic +/- methylmalonic aciduria (SUCLA2)
  • Mitochondrial DNA depletion syndrome 6, hepatocerebral type (MPV17)
  • Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
  • Mitochondrial DNA depletion syndrome 8A, encephalomyopathic type with renal tubulopathy (RRM2B)
  • Mitochondrial DNA depletion syndrome 8B, MNGIE type (RRM2B)
  • Mitochondrial DNA depletion syndrome 9, encephalomyopathic type + methylmalonic aciduria (SUCLG1)
  • Mitochondrial complex I deficiency, nuclear type 1 (NDUFS4)
  • Mitochondrial complex I deficiency, nuclear type 10 (NDUFAF2)
  • Mitochondrial complex I deficiency, nuclear type 11 (MDUFAF1)
  • Mitochondrial complex I deficiency, nuclear type 12 (NDUFA1)
  • Mitochondrial complex I deficiency, nuclear type 13 (NDUFA2)
  • Mitochondrial complex I deficiency, nuclear type 14 (NDUFA11)
  • Mitochondrial complex I deficiency, nuclear type 15 (MDUFAF4)
  • Mitochondrial complex I deficiency, nuclear type 16 (NDUFAF5)
  • Mitochondrial complex I deficiency, nuclear type 17 (NDUFAF6)
  • Mitochondrial complex I deficiency, nuclear type 18 (MDUFAF3)
  • Mitochondrial complex I deficiency, nuclear type 19 (FOXRED1)
  • Mitochondrial complex I deficiency, nuclear type 2 (NDUFS8)
  • Mitochondrial complex I deficiency, nuclear type 20 (ACAD9)
  • Mitochondrial complex I deficiency, nuclear type 22 (NDUFA10)
  • Mitochondrial complex I deficiency, nuclear type 26 (NDUFA9)
  • Mitochondrial complex I deficiency, nuclear type 27 (MTFMT)
  • Mitochondrial complex I deficiency, nuclear type 3 (NDUFS7)
  • Mitochondrial complex I deficiency, nuclear type 4 (NDUFV1)
  • Mitochondrial complex I deficiency, nuclear type 5 (NDUFS1)
  • Mitochondrial complex I deficiency, nuclear type 6 (NDUFS2)
  • Mitochondrial complex I deficiency, nuclear type 8 (NDUFS3)
  • Mitochondrial complex I deficiency, nuclear type 9 (MDUFS6)
  • Mitochondrial complex II deficiency, nuclear type 2 (SDHAF1)
  • Mitochondrial complex II deficiency, nuclear type 3 (SDHD)
  • Mitochondrial complex II deficiency, nuclear type 4 (SDHB)
  • Mitochondrial complex III deficiency, nuclear type 2 (TTC19)
  • Mitochondrial complex III deficiency, nuclear type 3 (UQCRB)
  • Mitochondrial complex III deficiency, nuclear type 4 (UQCRQ)
  • Mitochondrial complex IV deficiency (COX20)
  • Mitochondrial complex IV deficiency, nuclear type 1 (SURF1)
  • Mitochondrial complex IV deficiency, nuclear type 13 (COA6)
  • Mitochondrial complex IV deficiency, nuclear type 17 (COA8)
  • Mitochondrial complex IV deficiency, nuclear type 2 (SCO2)
  • Mitochondrial complex IV deficiency, nuclear type 21 (NDUFA4)
  • Mitochondrial complex IV deficiency, nuclear type 3 (COX10)
  • Mitochondrial complex IV deficiency, nuclear type 4 (SCO1)
  • Mitochondrial complex IV deficiency, nuclear type 5, French-Canadian (LRPPRC)
  • Mitochondrial complex IV deficiency, nuclear type 6 (COX15)
  • Mitochondrial complex IV deficiency, nuclear type 7 (COX6B1)
  • Mitochondrial complex IV deficiency, nuclear type 8 (TACO1)
  • Mitochondrial complex V, ATP synthase deficiency, nuclear type 1 (ATPAF2)
  • Mitochondrial complex V, ATP synthase deficiency, nuclear type 2 (TMEM70)
  • Mitochondrial complex V, ATP synthase deficiency, nuclear type 3 (ATP5E)
  • Mitochondrial complex V, ATP synthase deficiency, nuclear type 4 (ATP5F1A syn. ATP5A)
  • Mitochondrial encephalomyopathy w/combined respiratory chain deficiency (AIF1)
  • Mitochondrial myopathy with lactic acidosis (PET100)
  • Mitochondrial myopathy with lactic acidosis (PNPLA8)
  • Mitochondrial myopathy, episodic, optic atrophy + reversible leukoencephalopathy (FDX2 syn. FDX1L)
  • Mitochondrial phosphate carrier deficiency (SLC25A3)
  • Mitochondrial recessive ataxia syndrome [includes SANDO + SCAE] (POLG)
  • Mitochondrial respiratory chain complex II deficiency (SDHA)
  • Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1)
  • Multiple mitochondrial dysfunctions syndrome 3 (IBA57)
  • Multiple system atrophy, susceptibility to (COQ2)
  • Myopathy with extrapyramidal signs (MICU1)
  • Myopathy with lactic acidosis, hereditary (ISCU)
  • Myopathy, isolated mitochondrial, AD (CHCHD10)
  • Myopathy, lactic acidosis + sideroblastic anemia 1 (PUS1)
  • Myopathy, lactic acidosis + sideroblastic anemia 2 (YARS2)
  • Myopathy, mitochondrial + ataxia (MSTO1)
  • Myopathy, mitochondrial progressive, with congenital cataract + developmental delay (GFER)
  • Myopathy, vacuolar, with CASQ1 aggregates (CASQ1)
  • Neutral lipid storage disease with myopathy (PNPLA2)
  • Paraganglioma + gastric stromal sarcoma (SDHB, SDHC, SDHD)
  • Paragangliomas 1, with/-out deafness (SDHD)
  • Paragangliomas 2 (SDHAF2)
  • Paragangliomas 3 (SDHC)
  • Paragangliomas 4 (SDHB)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 3 (TWNK)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 2 (RNASEH1)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 4 (DGUOK, POLG2)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, AR 5 (TOP3A)
  • Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 (TK2)
  • Progressive external ophthalmoplegia, AD 1 (POLG)
  • Pyruvate dehydrogenase E1-alpha deficiency (PDHA1)
  • Pyruvate dehydrogenase E1-beta deficiency (PDHB)
  • Riboflavin deficiency (SLC52A1)
  • Sengers syndrome (AGK)
  • Spastic ataxia 5, AR (AFG3L2)
  • Spastic paraplegia 7, AR (SPG7)
  • Spinal muscular atrophy, Jokela type (CHCHD10)
  • Thiamine metabolism dysfunction syndrome 2, biotin-/thiamine-resp. encephalopathy type 2 (SLC19A3)
  • Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (TPK1)
Heredity, heredity patterns etc.
  • AD
  • AR
  • Mi
  • XL
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined