Multiple new genes have been added to our mitochondrial diseases nuclear gene set. Visit www.asperbio.com/asper-neurogenetics/mitochondrial-diseases/ to see the complete list of genes.
List of diseases covered by nuclear genes NGS panel
Published 30/05/2018List of diseases covered by
nuclear genes NGS panel
Gene | Condition |
AARS2 | Combined oxidative phosphorylation deficiency 8; Leukoencephalopathy, progressive, with ovarian failure |
ABCB7 | Anemia, sideroblastic, with ataxia |
ACAD9 | Mitochondrial complex I deficiency due to ACAD9 deficiency |
ACADM | Acyl-CoA dehydrogenase, medium chain, deficiency of |
ACADS | Acyl-CoA dehydrogenase, short-chain, deficiency of |
ACADVL | VLCAD deficiency |
ACO2 | Infantile cerebellar-retinal degeneration; Optic atrophy 9 |
AFG3L2 | Spastic ataxia 5, autosomal recessive; Spinocerebellar ataxia 28 |
AGK | Cataract 38, autosomal recessive; Sengers syndrome |
AIFM1 | Combined oxidative phosphorylation deficiency 6; Cowchock syndrome; Deafness, X-linked 5 |
ALAS2 | Anemia, sideroblastic, 1; Protoporphyria, erythropoietic, X-linked |
APTX | Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia |
ATPAF2 | Mitochondrial complex V (ATP synthase) deficiency, nuclear type 1 |
ATP7B | Wilson disease |
ATP5F1A | Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4; Combined oxidative phosphorylation deficiency 22 |
ATP5F1E | Mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 |
AUH | 3-methylglutaconic aciduria, type I |
BCS1L | Mitochondrial complex III deficiency, nuclear type 1; Bjornstad syndrome; GRACILE syndrome; Leigh syndrome |
BOLA3 | Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia |
CARS2 | Combined oxidative phosphorylation deficiency 27 |
CISD2 | Wolfram syndrome 2 |
COA5 | Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 |
COA6 | Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 |
COA8 | Mitochondrial complex IV deficiency |
C12orf65 | Combined oxidative phosphorylation deficiency 7; Spastic paraplegia 55, autosomal recessive |
C19orf12 | Neurodegeneration with brain iron accumulation 4; Spastic paraplegia 43, autosomal recessive |
COQ2 | Coenzyme Q10 deficiency, primary, 1; Multiple system atrophy, susceptibility to |
COQ6 | Coenzyme Q10 deficiency, primary, 6 |
COQ9 | Coenzyme Q10 deficiency, primary, 5 |
COQ8A | Coenzyme Q10 deficiency, primary, 4 |
COX10 | Mitochondrial complex IV deficiency; Leigh syndrome due to mitochondrial COX4 deficiency |
COX14 | Mitochondrial complex IV deficiency |
COX15 | Leigh syndrome due to cytochrome c oxidase deficiency; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 |
COX20 | Mitochondrial complex IV deficiency |
COX6A1 | Charcot-Marie-Tooth disease, recessive intermediate D |
COX6A2 | Mitochondrial complex IV deficiency |
COX8A2 | Mitochondrial complex IV deficiency |
COX6B1 | Mitochondrial complex IV deficiency |
CPT1A | CPT deficiency, hepatic, type IA |
CPT2 | CPT II deficiency, infantile; CPT II deficiency, lethal neonatal; CPT II deficiency, myopathic, stress-induced |
CYC1 | Mitochondrial complex III deficiency, nuclear type 6 |
DARS2 | Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation |
DGUOK | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type); Portal hypertension, noncirrhotic; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 |
DLAT | Pyruvate dehydrogenase E2 deficiency |
DLD | Dihydrolipoamide dehydrogenase deficiency |
DNA2 | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6; Seckel syndrome 8 |
DNAJC19 | 3-methylglutaconic aciduria, type V |
DNM1L | Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1; Optic atrophy 5 |
ECHS1 | Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency |
ELAC2 | Combined oxidative phosphorylation deficiency 17 |
ETFA | Glutaric acidemia IIA |
EARS2 | Combined oxidative phosphorylation deficiency 12 |
ETFB | Glutaric acidemia IIB |
ETFDH | Glutaric acidemia IIC |
ETHE1 | Ethylmalonic encephalopathy |
FARS2 | Combined oxidative phosphorylation deficiency 14; Spastic paraplegia 77, autosomal recessive |
FASTKD2 | Mitochondrial complex IV deficiency |
FBP1 | Fructose-1,6-bisphosphatase deficiency |
FBXL4 | Mitochondrial DNA depletion syndrome 13 |
FH | Fumarase deficiency; Leiomyomatosis and renal cell cancer |
FDX2 | Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy |
FLAD1 | Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency |
FOXRED1 | Leigh syndrome due to mitochondrial complex I deficiency; Mitochondrial complex I deficiency |
GAMT | Cerebral creatine deficiency syndrome 2 |
GARS1 | Neuronopathy, distal hereditary motor, type VA; Charcot-Marie-Tooth disease, type 2D |
GATM | Cerebral creatine deficiency syndrome 3 |
GCDH | Glutaricaciduria, type I |
GFER | Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay |
GFM1 | Combined oxidative phosphorylation deficiency 1 |
GFM2 | Combined oxidative phosphorylation deficiency 39 |
GLRX5 | Spasticity, childhood-onset, with hyperglycinemia; Anemia, sideroblastic, 3, pyridoxine-refractory |
G6PC | Glycogen storage disease Ia |
GTPBP3 | Combined oxidative phosphorylation deficiency 23 |
GYS2 | Glycogen storage disease 0, liver |
HADH | 3-hydroxyacyl-CoA dehydrogenase deficiency; Hyperinsulinemic hypoglycemia, familial, 4 |
HADHA | LCHAD deficiency; Trifunctional protein deficiency |
HARS2 | Perrault syndrome 2 |
HLCS | Holocarboxylase synthetase deficiency |
HMGCL | HMG-CoA lyase deficiency |
HSPD1 | Leukodystrophy, hypomyelinating, 4; Spastic paraplegia 13, autosomal dominant |
HTRA2 | 3-methylglutaconic aciduria, type VIII |
ISCU | Myopathy with lactic acidosis, hereditary |
LRPPRC | Leigh syndrome, French-Canadian type |
MFN2 | Charcot-Marie-Tooth disease, axonal, type 2A2A; Charcot-Marie-Tooth disease, axonal, type 2A2B; Hereditary motor and sensory neuropathy VIA |
MPV17 | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) |
MRPS7 | Combined oxidative phosphorylation deficiency 34 |
MRPS16 | Combined oxidative phosphorylation deficiency 2 |
MRPS22 | Combined oxidative phosphorylation deficiency 5 |
MTFMT | Combined oxidative phosphorylation deficiency 15 |
MTO1 | Combined oxidative phosphorylation deficiency 10 |
MTPAP | Spastic ataxia 4, autosomal recessive |
NARS2 | Combined oxidative phosphorylation deficiency 24; Deafness, autosomal recessive 94 |
NDUFA1 | Mitochondrial complex I deficiency |
NDUFA9 | Mitochondrial complex I deficiency, nuclear type 26 |
NDUFA10 | Leigh syndrome |
NDUFA11 | Mitochondrial complex I deficiency |
NDUFA12 | Leigh syndrome due to mitochondrial complex 1 deficiency |
NDUFA2 | Leigh syndrome due to mitochondrial complex I deficiency |
NDUFAF1 | Mitochondrial complex I deficiency |
NDUFAF2 | Mitochondrial complex I deficiency |
NDUFAF3 | Mitochondrial complex I deficiency |
NDUFAF4 | Mitochondrial complex I deficiency |
NDUFAF5 | Mitochondrial complex 1 deficiency |
NDUFAF6 | Mitochondrial complex I deficiency, nuclear type 17 |
NDUFB3 | Mitochondrial complex I deficiency |
NDUFB9 | Mitochondrial complex I deficiency |
NDUFB11 | Mitochondrial complex I deficiency, nuclear type 30; Linear skin defects with multiple congenital anomalies 3 |
NDUFS1 | Mitochondrial complex I deficiency |
NDUFS2 | Mitochondrial complex I deficiency |
NDUFS3 | Leigh syndrome due to mitochondrial complex I deficiency; Mitochondrial complex I deficiency |
NDUFS4 | Leigh syndrome; Mitochondrial complex I deficiency |
NDUFS6 | Mitochondrial complex I deficiency |
NDUFS7 | Leigh syndrome |
NDUFS8 | Leigh syndrome due to mitochondrial complex I deficiency |
NDUFV1 | Mitochondrial complex I deficiency |
NDUFV2 | Mitochondrial complex I deficiency |
NFU1 | Multiple mitochondrial dysfunctions syndrome 1 |
NR2F1 | Bosch-Boonstra-Schaaf optic atrophy syndrome |
NUBPL | Mitochondrial complex I deficiency |
OPA1 | Mitochondrial DNA depletion syndrome 14; Behr syndrome; Optic atrophy 1; Optic atrophy plus syndrome |
OPA3 | 3-methylglutaconic aciduria, type III; Optic atrophy 3 with cataract |
OTC | Ornithine transcarbamylase deficiency |
PARS2 | Epileptic encephalopathy, early infantile, 75 |
PC | Pyruvate carboxylase deficiency |
PCCA | Propionicacidemia |
PCCB | Propionicacidemia |
PDHA1 | Pyruvate dehydrogenase E1-alpha deficiency |
PDHB | Pyruvate dehydrogenase E1-beta deficiency |
PDHX | Lacticacidemia due to PDX1 deficiency |
PDP1 | Pyruvate dehydrogenase phosphatase deficiency |
PDSS1 | Coenzyme Q10 deficiency, primary, 2 |
PDSS2 | Coenzyme Q10 deficiency, primary, 3 |
PDX1 | MODY, type IV; Pancreatic agenesis 1 |
PET100 | Mitochondrial complex IV deficiency |
PNPT1 | Combined oxidative phosphorylation deficiency 13; Deafness, autosomal recessive 70 |
POLG | Mitochondrial DNA depletion syndrome 4A (Alpers type); Mitochondrial DNA depletion syndrome 4B (MNGIE type); Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE); Progressive external ophthalmoplegia, autosomal dominant 1; Progressive external ophthalmoplegia, autosomal recessive 1 |
POLG2 | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 |
PUS1 | Myopathy, lactic acidosis, and sideroblastic anemia 1 |
RARS2 | Pontocerebellar hypoplasia, type 6 |
REEP1 | Neuronopathy, distal hereditary motor, type VB; Spastic paraplegia 31, autosomal dominant |
RMND1 | Combined oxidative phosphorylation deficiency 11 |
RNASEH1 | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 |
RRM2B | Mitochondrial DNA depletion syndrome 8A ; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5 |
SARS2 | Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis |
SCO1 | Mitochondrial complex IV deficiency |
SCO2 | Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1; Myopia 6 |
SDHA | Mitochondrial respiratory chain complex II deficiency; Leigh syndrome; Cardiomyopathy, dilated, 1GG; Paragangliomas 5 |
SDHAF1 | Mitochondrial complex II deficiency |
SERAC1 | 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome |
SETX | Amyotrophic lateral sclerosis 4, juvenile; Spinocerebellar ataxia, autosomal recessive 1 |
SFXN4 | Combined oxidative phosphorylation deficiency 18 |
SLC19A3 | Thiamine metabolism dysfunction syndrome 2 |
SLC25A3 | Mitochondrial phosphate carrier deficiency |
SLC25A4 | Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD; Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 |
SLC25A20 | Carnitine-acylcarnitine translocase deficiency |
SLC25A26 | Combined oxidative phosphorylation deficiency 28 |
SLC25A38 | Anemia, sideroblastic, 2, pyridoxine-refractory |
SLC25A46 | Neuropathy, hereditary motor and sensory, type VIB |
SLC6A8 | Cerebral creatine deficiency syndrome 1 |
SLC37A4 | Glycogen storage disease Ib; Glycogen storage disease Ic |
SOD1 | Amyotrophic lateral sclerosis 1 |
SPAST | Spastic paraplegia 4, autosomal dominant |
SPG7 | Spastic paraplegia 7, autosomal recessive |
SUCLA2 | Mitochondrial DNA depletion syndrome 5 |
SUCLG1 | Mitochondrial DNA depletion syndrome 9 |
SURF1 | Charcot-Marie-Tooth disease, type 4K; Leigh syndrome, due to COX IV deficiency |
TACO1 | Mitochondrial complex IV deficiency |
TARS2 | Combined oxidative phosphorylation deficiency 21 |
TAZ | Barth syndrome |
TFAM | Mitochondrial DNA depletion syndrome 15 |
TIMM8A | Mohr-Tranebjaerg syndrome |
TK2 | Mitochondrial DNA depletion syndrome 2; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 |
TMEM70 | Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 |
TMEM126A | Optic atrophy 7 |
TMEM126B | Mitochondrial complex I deficiency, nuclear type 29 |
TPK1 | Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) |
TRIT1 | Combined oxidative phosphorylation deficiency 35 |
TRMT10C | Combined oxidative phosphorylation deficiency 30 |
TRMU | Liver failure, transient infantile; Deafness, mitochondrial, modifier of |
TRNT1 | Retinitis pigmentosa and erythrocytic microcytosis; Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay |
TSFM | Combined oxidative phosphorylation deficiency 3 |
TTC19 | Mitochondrial complex III deficiency, nuclear type 2 |
TUFM | Combined oxidative phosphorylation deficiency 4 |
TWNK | Mitochondrial DNA depletion syndrome 7; Perrault syndrome 5; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 |
TYMP | Mitochondrial DNA depletion syndrome 1 (MNGIE type) |
UQCC2 | Mitochondrial complex III deficiency, nuclear type 7 |
UQCC3 | Mitochondrial complex III deficiency, nuclear type 9 |
UQCRC2 | Mitochondrial complex III deficiency, nuclear type 5 |
UQCRB | Mitochondrial complex III deficiency, nuclear type 3 |
UQCRQ | Mitochondrial complex III deficiency, nuclear type 4 |
VARS2 | Combined oxidative phosphorylation deficiency 20 |
WFS1 | Deafness, autosomal dominant 6/14/38; Wolfram syndrome 1; Wolfram-like syndrome, autosomal dominant; Cataract 41; Diabetes mellitus, noninsulin-dependent, association with |
YARS2 | Myopathy, lactic acidosis, and sideroblastic anemia 2 |
Mitochondrial Diseases
Published 02/06/2015Mitochondrial Diseases
Mitochondrial genome sequencing
Lab method: | Next generation sequencing Heteroplasmy less than 20% is not detectable by sequencing. |
TAT: | 2-4 weeks |
Specimen requirements: | 2-4 ml of blood with anticoagulant EDTA
1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl 50-75 mg fresh frozen tissue (in case suspected mtDNA mutations may not be detected in DNA extracted from blood) |
Ordering information: | Go to online ordering or download sample submission form |
Nuclear genes NGS panel
Genes (full coding region): |
AARS2, ABCB7, ACAD9, ACADL, ACADM, ACADS, ACADVL, ACO2, AFG3L2, AGK, AIFM1, ALAS2, APTX, ATPAF2, ATP7B, ATP5F1A, ATP5F1E, AUH, BCS1L, BOLA3, CARS2, C12orf65, C19orf12, CISD2, COA3, COA5, COA6, COA8 (APOPT1), COQ2, COQ6, COQ9, COQ8A, COX10, COX14, COX15, COX20, COX8A, COX6A1, COX6A2, COX6B1, COX4I1, CPT1A, CPT2, CYC1, DARS2, DGUOK, DLAT, DLD, DNA2, DNAJC19, DNM1L, EARS2, ECHS1, ELAC2, ETFA, ETFB, ETFDH, ETHE1, FARS2, FASTKD2, FBP1, FBXL4, FDX2 (FDX1L), FH, FLAD1, FOXRED1, G6PC, GAMT, GARS1 (GARS), GATM, GCDH, GFER, GFM1, GFM2, GLRX5, GTPBP3, GYS2, HARS2, HLCS, HADH, HADHA, HMGCL, HSPD1, HTRA2, IARS2, IBA57, ISCA2, ISCU, LAMP2, LARS1, LARS2, LIAS, LIPT1, LRPPRC, LYRM4, LYRM7, MARS2, MFF, MFN2, MGME1, MICU1, MPC1, MPV17, MRPL12, MRPL3, MRPL44, MRPS7, MRPS16, MRPS22, MTFMT, MTO1, MTPAP, NARS2, NDUFA1, NDUFA4, NDUFA9, NDUFA10, NDUFA11, NDUFA12, NDUFA2, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFAF7, NDUFB3, NDUFB9, NDUFB11, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NFS1, NFU1, NR2F1, NUBPL, OPA1, OPA3, OTC, PARS2, PC, PCCA, PCCB, PDHA1, PDHB, PDHX, PDP1, PDSS1, PDSS2, PDX1, PET100, PNPT1, POLG, POLG2, PUS1, RARS2, REEP1, RMND1, RNASEH1, RRM2B, SARS2, SCO1, SCO2, SDHA, SDHAF1, SERAC1, SETX, SFXN4, SLC6A8, SLC19A3, SLC25A3, SLC25A20, SLC25A4, SLC25A26, SLC25A38, SLC25A46, SLC37A4, SOD1, SPAST, SPG7, SUCLA2, SUCLG1, SURF1,TACO1, TARS2, TAZ, TFAM , TIMM8A, TK2, TMEM126A, TMEM126B, TMEM70, TPK1, TRIT1, TRMT10C, TRMU, TRNT1, TSFM, TTC19, TUFM, TWNK, TYMP, UQCC2, UQCC3, UQCRB, UQCRC2, UQCRQ, VARS2, WFS1, YARS2 |
Lab method: | NGS panel with CNV analysis |
TAT: | 6-9 weeks |
Specimen requirements: | 2-4 ml of blood with anticoagulant EDTA
1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl |
Ordering information: | Go to online ordering or download sample submission form |
Single gene sequencing
Genes: | ACADS, ACADVL |
Lab method: | Sanger sequencing, next generation sequencing |
TAT: | 2-4 weeks |
Specimen requirements: | 2-4 ml of blood with anticoagulant EDTA
2 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl |
Ordering information: | Go to online ordering or download sample submission form |
MELAS Syndrome targeted mutation analysis
Genes: | MT-TL1 |
No of detectable markers: |
1 (m.3243A>G) |
Lab method: | Sanger sequencing |
TAT: | 1-2 weeks |
Specimen requirements: | 2-4 ml of blood with anticoagulant EDTA
120 ng DNA in TE, AE or pure sterile water at 100-250 ng/µl |
Ordering information: | Go to online ordering or download sample submission form |
Deletion/duplication analysis
Genes: | DGUOK, MPV17, POLG, POLG2, RRM2B, SLC25A4, SUCLA2, SUCLG1, TK2, TWNK |
Lab method: | MLPA |
TAT: | 4-6 weeks |
Specimen requirements: | 2-4 ml of blood with anticoagulant EDTA
2 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl |
Ordering information: | Go to online ordering or download sample submission form |
Indications for genetic testing:
1. Diagnosis of patients with phenotype characteristic for mitochondrial disease
2. Diagnosis of patients with family history suggestive for mitochondrial disease
3. Genetic counseling of individuals with mitochondrial disease and affected family members
Mitochondrial diseases are a genetically and clinically heterogeneous group of disorders that arise as a consequence of dysfunction of the mitochondrial respiratory chain. The estimate for the prevalence of all mitochondrial disorders 1:8500, but they are thought to be greatly under-diagnosed. Mitochondrial disorders can be caused by mutations of nuclear or mitochondrial DNA (mtDNA). If nuclear gene defects may be inherited in an autosomal recessive or autosomal dominant manner, mtDNA defects are transmitted only maternally. As the female could have heteroplasmic mtDNA mutations, which could be transmitted unequally to her offspring, the sibs could exhibit considerable clinical variability.
Symptoms of the mitochondrial disease can begin at any age. Mitochondrial disorders may affect a single organ (e.g. Leber hereditary optic neuropathy, LHON) or involve multiple organ systems (e.g. Myoclonic epilepsy with ragged-red fibers, MERRF). Common clinical features of mitochondrial disorder include, for example muscle weakness, exercise intolerance, trouble with balance and coordination, sensorineural deafness, impaired vision, seizures and learning deficits, cardiomyopathy, diabetes mellitus, stunted growth, and a high incidence of mid- and late pregnancy loss.
References:
Wallace DC. Mitochondrial diseases in man and mouse. Science. 1999;283:1482–8.
Chinnery PF. Mitochondrial Disorders Overview. Pagon RA, Adam MP, Bird TD, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2013.
DiMauro S, Schon EA. Nuclear power and mitochondrial disease. Nat Genet. 1998;19:214–5.
Leonard JV, Schapira AVH. Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet. 2000a;355:299–304.
Leonard JV, Schapira AVH. Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet. 2000b;355:389–94.
Panel of Mitochondrial Diseases at Asper Biotech
Published 04/12/2013A new testing panel targeted to mitochondrial diseases is now available. The testing panel combines NGS, Sanger sequencing, and aCGH technology to examine alterations in mitochondrial genes, as well as in nuclear genes associated with mitochondrial disorders.
The tests can be ordered separately or as a set of several tests according to specific indications. Ordering the set of tests gives 10% discount from the total price. Learn more: https://www.asperbio.com/mitochondrial-diseases