List of diseases covered by nuclear genes NGS panel

Published 30/05/2018

List 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 02/06/2015

Mitochondrial 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
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.

50-75 mg fresh frozen tissue (in case suspected mtDNA mutations may not be detected in DNA extracted from blood)
Tissue should be frozen immediately at collection, stored at -80°C and shipped on dry ice.
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

List of diseases covered by the panel
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
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
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
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
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
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
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
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
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 04/12/2013

A 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