MCID: MTC056
MIFTS: 51

Mitochondrial Dna Depletion Syndrome 4a

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Liver diseases, Metabolic diseases, Endocrine diseases

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 4a

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 4a:

Name: Mitochondrial Dna Depletion Syndrome 4a 57 12 12 75 13
Alpers Syndrome 57 12 53 25 59 75 37 55 15 73
Alpers-Huttenlocher Syndrome 57 12 53 25 59 75
Alpers Progressive Infantile Poliodystrophy 57 12 53 25 75
Progressive Sclerosing Poliodystrophy 12 25 54 29 6
Alpers Diffuse Degeneration of Cerebral Gray Matter with Hepatic Cirrhosis 57 53 25 75
Alpers Disease 76 53 25
Pndc 57 53 75
Neuronal Degeneration of Childhood with Liver Disease, Progressive 57 53
Diffuse Cerebral Sclerosis of Schilder 25 73
Mtdps4a 57 75
Neuronal Degeneration of Childhood with Liver Disease, Progressive; Pndc 57
Progressive Neuronal Degeneration of Childhood with Liver Disease 59
Neuronal Degeneration of Childhood with Liver Disease Progressive 75
Mitochondrial Dna Depletion Syndrome 4a Alpers Type 75
Alpers Progressive Sclerosing Poliodystrophy 59
Alpers' Disease or Gray-Matter Degeneration 12
Diffuse Cerebral Degeneration in Infancy 53
Thyroid-Stimulating Hormone Level Qtl 1 13
Poliodystrophia Cerebri Progressiva 53
Progressive Cerebral Poliodystrophy 53
Infantile Poliodystrophy 53
Alper's Syndrome 12
Ahs 75

Characteristics:

Orphanet epidemiological data:

59
alpers-huttenlocher syndrome
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: adolescent,adult,late childhood,young Adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
rapidly progressive
onset in infancy after normal birth and neonatal period
death usually by age 3 years
later onset (late childhood to young adult) has been reported
increased sensitivity to valproic acid toxicity


HPO:

32
mitochondrial dna depletion syndrome 4a:
Onset and clinical course rapidly progressive infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 4a

NINDS : 54 Alpers' disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome characterized by three co-occurring clinical symptoms: psychomotor regression (dementia); seizures; and liver disease.  It is an autosomal recessive disease caused by mutation in the gene for the mitochondrial DNA polymerase POLG.  The disease occurs in about one in 100,000 persons.  Most individuals with Alpers' disease do not show symptoms at birth and develop normally for weeks to years before the onset of symptoms.  Diagnosis is established by testing for the POLG gene.  Symptoms typically occur months before tissue samples show the mitochondrial DNA depletion, so that these depletion studies cannot be used for early diagnosis.  About 80 percent of individuals with Alpers' disease develop symptoms in the first two years of life, and 20 percent develop symptoms between ages 2 and 25.  The first symptoms of the disorder are usually nonspecific and may include hypoglycemia secondary to underlying liver disease, failure to thrive, infection-associated encephalopathy, spasticity, myoclonus (involuntary jerking of a muscle or group of muscles), seizures, or liver failure.  An increased protein level is seen in cerebrospinal fluid analysis.  Cortical blindness (loss of vision due to damage to the area of the cortex that controls vision) develops in about 25 percent of cases. Gastrointestinal dysfunction and cardiomyopathy may occur.  Dementia is typically episodic and often associated with an infection that occurs while another disease is in process.  Seizures may be difficult to control and unrelenting seizures can cause developmental regression as well.  "Alpers-like" disorders  without liver disease are genetically different and have a different clinical course.  Fewer than one-third of individuals with the "Alpers-like" phenotype without liver disease have POLG mutations.

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 4a, also known as alpers syndrome, is related to ah amyloidosis and thyroid-stimulating hormone level quantitative trait locus 1, and has symptoms including convulsions, ataxia and myoclonus. An important gene associated with Mitochondrial Dna Depletion Syndrome 4a is POLG (DNA Polymerase Gamma, Catalytic Subunit), and among its related pathways/superpathways is Mitochondrial Gene Expression. Affiliated tissues include liver, brain and cortex, and related phenotypes are ataxia and muscular hypotonia

Disease Ontology : 12 A cerebral degeneration that results in progressive degeneration of grey matter in the cerebrum and has symptom convulsions.

Genetics Home Reference : 25 Alpers-Huttenlocher syndrome is one of the most severe of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Alpers-Huttenlocher syndrome typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease.

NIH Rare Diseases : 53 Alpers syndrome is a progressive neurologic disorder that begins during childhood and is complicated in many instances by serious liver disease. Symptoms include increased muscle tone with exaggerated reflexes (spasticity), seizures, and loss of cognitive ability (dementia).   Most often Alpers syndrome is caused by mutations in the POLG gene.

OMIM : 57 Mitochondrial DNA depletion syndrome-4A, also known as Alpers syndrome, is an autosomal recessive disorder characterized by a clinical triad of psychomotor retardation, intractable epilepsy, and liver failure in infants and young children. Pathologic findings include neuronal loss in the cerebral gray matter with reactive astrocytosis and liver cirrhosis. The disorder is progressive and often leads to death from hepatic failure or status epilepticus before age 3 years (review by Milone and Massie, 2010). Some affected individuals may show mild intermittent 3-methylglutaconic aciduria and defects in mitochondrial oxidative phosphorylation (Wortmann et al., 2009). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Neuropathologic changes characteristic of Alpers syndrome, namely laminar cortical necrosis, may also be seen in some patients with combined oxidative phosphorylation deficiency-14 (COXPD14; 614946), caused by mutation in the FARS2 gene (611592), and COXPD24 (616239), caused by mutation in the NARS2 gene (612803). (203700)

UniProtKB/Swiss-Prot : 75 Mitochondrial DNA depletion syndrome 4A: An autosomal recessive hepatocerebral syndrome due to mitochondrial dysfunction. The typical course of the disease includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.

Wikipedia : 76 Mitochondrial DNA depletion syndrome (MDS or MDDS) is any of a group of autosomal recessive disorders... more...

Related Diseases for Mitochondrial Dna Depletion Syndrome 4a

Diseases related to Mitochondrial Dna Depletion Syndrome 4a via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 64)
# Related Disease Score Top Affiliating Genes
1 ah amyloidosis 12.1
2 thyroid-stimulating hormone level quantitative trait locus 1 11.5
3 adrenoleukodystrophy 11.5
4 tumefactive multiple sclerosis 11.5
5 sudanophilic cerebral sclerosis 11.3
6 pelizaeus-merzbacher disease 11.3
7 balo concentric sclerosis 11.3
8 myelinoclastic diffuse sclerosis 11.3
9 hypotrichosis 7 11.2
10 hemophilia 11.1
11 combined oxidative phosphorylation deficiency 24 11.1
12 atrial standstill 1 11.0
13 combined oxidative phosphorylation deficiency 14 10.9
14 hemochromatosis, type 1 10.9
15 aplastic anemia 10.9
16 hemolytic anemia 10.9
17 primary ciliary dyskinesia 10.9
18 atrial fibrillation 10.9
19 long qt syndrome 10.9
20 adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency 10.9
21 adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency 10.9
22 adrenal hyperplasia, congenital, due to steroid 11-beta-hydroxylase deficiency 10.9
23 adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiency 10.9
24 pulmonary fibrosis, idiopathic 10.8
25 polycythemia vera 10.8
26 abdominal obesity-metabolic syndrome 1 10.8
27 bronchopulmonary dysplasia 10.8
28 thrombocytopenia 10.8
29 sleep apnea 10.8
30 thrombotic thrombocytopenic purpura 10.8
31 thrombocytopenia due to platelet alloimmunization 10.8
32 pneumonia 10.8
33 lymphopenia 10.8
34 alien hand syndrome 10.8
35 ataxia neuropathy spectrum 10.0 POLG TWNK
36 maternally-inherited progressive external ophthalmoplegia 10.0 POLG TWNK
37 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 10.0 POLG TWNK
38 hepatitis 9.9
39 neuronitis 9.9
40 diabetic polyneuropathy 9.9 POLG TWNK
41 mitochondrial dna depletion syndrome 3 9.9 DGUOK TWNK
42 myoclonic epilepsy associated with ragged-red fibers 9.8 POLG TWNK
43 mitochondrial neurogastrointestinal encephalopathy disease 9.8 POLG TYMP
44 cerebral degeneration 9.8
45 cerebritis 9.8
46 mitochondrial neurogastrointestinal encephalomyopathy 9.8 POLG TYMP
47 creutzfeldt-jakob disease 9.8
48 autoimmune hepatitis 9.8
49 liver disease 9.8
50 status epilepticus 9.8

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 4a:



Diseases related to Mitochondrial Dna Depletion Syndrome 4a

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 4a

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
ataxia
hypertonia
myoclonus
paralysis
dementia
more
Abdomen Liver:
hepatomegaly
micronodular cirrhosis
liver failure
biopsy shows microvesicular steatosis
hepatocyte dropout
more
Laboratory Abnormalities:
increased serum lactate
increased csf protein
elevated liver function tests
decreased dna polymerase-gamma (polg, ) activity
intermittent 3-methylglutaconic aciduria
more
Head And Neck Eyes:
loss of vision
visual disturbances
cortical blindness
abnormal visual evoked potential (vep)

Growth Other:
failure to thrive

Abdomen Gastrointestinal:
vomiting

Muscle Soft Tissue:
hypotonia
decreased mitochondrial respiratory chain complex activity
mitochondrial dna depletion


Clinical features from OMIM:

203700

Symptoms:

12
  • convulsions

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 4a:

59 32 (show all 45)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
2 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
3 developmental regression 59 32 frequent (33%) Frequent (79-30%) HP:0002376
4 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
5 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
6 blindness 59 32 occasional (7.5%) Occasional (29-5%) HP:0000618
7 myoclonus 59 32 frequent (33%) Frequent (79-30%) HP:0001336
8 generalized tonic-clonic seizures 59 32 frequent (33%) Frequent (79-30%) HP:0002069
9 coma 59 32 frequent (33%) Frequent (79-30%) HP:0001259
10 areflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001284
11 choreoathetosis 59 32 frequent (33%) Frequent (79-30%) HP:0001266
12 focal seizures 59 32 frequent (33%) Frequent (79-30%) HP:0007359
13 progressive spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0002191
14 spastic paraparesis 59 32 frequent (33%) Frequent (79-30%) HP:0002313
15 spasticity 59 Frequent (79-30%)
16 failure to thrive 32 HP:0001508
17 hepatomegaly 32 HP:0002240
18 abnormality of visual evoked potentials 32 HP:0000649
19 hypertonia 32 HP:0001276
20 vomiting 32 HP:0002013
21 abnormality of the eye 59 Frequent (79-30%)
22 abnormality of vision 59 Frequent (79-30%)
23 abnormality of movement 59 Frequent (79-30%)
24 elevated hepatic transaminases 32 HP:0002910
25 increased serum lactate 32 HP:0002151
26 visual loss 32 HP:0000572
27 paralysis 32 HP:0003470
28 dementia 32 HP:0000726
29 hepatic failure 32 HP:0001399
30 cerebellar atrophy 32 HP:0001272
31 astrocytosis 32 HP:0002446
32 status epilepticus 32 HP:0002133
33 generalized hypotonia 32 HP:0001290
34 paraparesis 59 Frequent (79-30%)
35 increased csf protein 32 HP:0002922
36 neuronal loss in central nervous system 32 HP:0002529
37 gliosis 32 HP:0002171
38 cortical visual impairment 32 HP:0100704
39 microvesicular hepatic steatosis 32 HP:0001414
40 3-methylglutaconic aciduria 32 HP:0003535
41 micronodular cirrhosis 32 HP:0001413
42 ethylmalonic aciduria 32 HP:0003219
43 bile duct proliferation 32 HP:0001408
44 epilepsia partialis continua 32 HP:0012847
45 cerebral cortical neurodegeneration 32 HP:0006964

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 4a:


ataxia, myoclonus, vomiting, visual disturbance, unspecified visual loss

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 4a

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Alpers Huttenlocher Natural History Study Recruiting NCT03034512
2 Combination of Multiparametric MRI and Electrophysiology for the Development of New Biomarkers in Spinal Cord Diseases Recruiting NCT02885870 Not Applicable
3 Prehospital Resuscitation Intranasal Cooling Effects Seen in MRI of the Brain After Cardiac Arrest Terminated NCT02179060

Search NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 4a

Genetic Tests for Mitochondrial Dna Depletion Syndrome 4a

Genetic tests related to Mitochondrial Dna Depletion Syndrome 4a:

# Genetic test Affiliating Genes
1 Progressive Sclerosing Poliodystrophy 29 POLG

Anatomical Context for Mitochondrial Dna Depletion Syndrome 4a

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 4a:

41
Liver, Brain, Cortex, Testes, Thyroid, Eye, Spinal Cord

Publications for Mitochondrial Dna Depletion Syndrome 4a

Articles related to Mitochondrial Dna Depletion Syndrome 4a:

(show all 35)
# Title Authors Year
1
Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome. ( 25629079 )
2015
2
Valproic acid-induced hepatotoxicity in alpers syndrome is associated with mitochondrial permeability transition pore opening-dependent apoptotic sensitivity in an induced pluripotent stem cell model. ( 25605636 )
2015
3
Abnormalities in Glycogen Metabolism in a Patient with Alpers' Syndrome Presenting with Hypoglycemia. ( 24272679 )
2013
4
Alpers syndrome: an unusual etiology of failure to thrive. ( 22849523 )
2012
5
Alpers syndrome: the natural history of a case highlighting neuroimaging, neuropathology, and fat metabolism. ( 22114215 )
2012
6
Polymerase gamma deficiency (POLG): clinical course in a child with a two stage evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and neuropathological findings of Leigh's encephalopathy. ( 22342071 )
2012
7
Complete Deletion of a POLG1 Allele in a Patient with Alpers Syndrome. ( 23430898 )
2012
8
Phenotypic and genotypic variability in Alpers syndrome. ( 22237560 )
2012
9
POLG exon 22 skipping induced by different mechanisms in two unrelated cases of Alpers syndrome. ( 20691285 )
2011
10
Application of oligonucleotide array CGH in the detection of a large intragenic deletion in POLG associated with Alpers Syndrome. ( 20708716 )
2011
11
Gender variability in presentation with Alpers' syndrome: a report of eight patients from the UAE. ( 21305355 )
2011
12
Alpers syndrome with mutations in POLG: clinical and investigative features. ( 22000311 )
2011
13
Molecular and biochemical characterisation of a novel mutation in POLG associated with Alpers syndrome. ( 21235791 )
2011
14
Alpers syndrome presenting with anatomopathological features of fulminant autoimmune hepatitis. ( 20582478 )
2010
15
Juvenile-onset Alpers syndrome: interpreting MRI findings. ( 20385895 )
2010
16
Proof of progression over time: finally fulminant brain, muscle, and liver affection in Alpers syndrome associated with the A467T POLG1 mutation. ( 18783964 )
2009
17
De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome. ( 19501198 )
2009
18
Alpers syndrome with prominent white matter changes. ( 17923349 )
2008
19
Rapidly progressive neurological deterioration in a child with Alpers syndrome exhibiting a previously unremarkable brain MRI. ( 18991199 )
2008
20
Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus. ( 18294203 )
2008
21
Molecular diagnosis of Alpers syndrome. ( 16545482 )
2006
22
Alpers syndrome: progressive neuronal degeneration of children with liver disease. ( 17109792 )
2006
23
Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome. ( 16181814 )
2005
24
POLG mutations associated with Alpers syndrome and mitochondrial DNA depletion. ( 16130100 )
2005
25
POLG mutations and Alpers syndrome. ( 15929042 )
2005
26
POLG mutations in Alpers syndrome. ( 16177225 )
2005
27
POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. ( 15122711 )
2004
28
Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers' syndrome? An analysis of a national surveillance study. ( 15146014 )
2004
29
Mitochondrial DNA depletion in Alpers syndrome. ( 15328560 )
2004
30
Respiratory chain deficiency in Alpers syndrome. ( 11521212 )
2001
31
Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome. ( 9894877 )
1999
32
[Neurophysiological study in Alpers syndrome]. ( 9533210 )
1998
33
Brain MR imaging findings in two patients with Alpers' syndrome. ( 8959359 )
1996
34
Alpers' syndrome presenting with seizures and multiple stroke-like episodes in a 17-year-old male. ( 8605737 )
1995
35
Progressive neuronal degeneration of childhood (Alpers syndrome) with hepatic cirrhosis. ( 8444257 )
1993

Variations for Mitochondrial Dna Depletion Syndrome 4a

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 4a:

75 (show all 16)
# Symbol AA change Variation ID SNP ID
1 POLG p.Ala467Thr VAR_012155 rs113994095
2 POLG p.Thr251Ile VAR_023664 rs113994094
3 POLG p.Pro587Leu VAR_023671 rs113994096
4 POLG p.Gly848Ser VAR_023675 rs113994098
5 POLG p.Arg232Gly VAR_058870
6 POLG p.Leu244Pro VAR_058872
7 POLG p.Ala767Asp VAR_058886
8 POLG p.Gln879His VAR_058890
9 POLG p.Thr885Ser VAR_058891
10 POLG p.Thr914Pro VAR_058892 rs139590686
11 POLG p.Ala957Pro VAR_058893
12 POLG p.Arg1096His VAR_058894 rs368435864
13 POLG p.His1110Tyr VAR_058895
14 POLG p.His1134Arg VAR_058896
15 POLG p.Lys1191Asn VAR_058898
16 POLG p.Glu1136Lys VAR_065092 rs56047213

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 4a:

6
(show top 50) (show all 315)
# Gene Variation Type Significance SNP ID Assembly Location
1 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic rs113994095 GRCh37 Chromosome 15, 89870432: 89870432
2 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic rs113994095 GRCh38 Chromosome 15, 89327201: 89327201
3 POLG NM_002693.2(POLG): c.911T> G (p.Leu304Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918044 GRCh37 Chromosome 15, 89872286: 89872286
4 POLG NM_002693.2(POLG): c.911T> G (p.Leu304Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918044 GRCh38 Chromosome 15, 89329055: 89329055
5 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh37 Chromosome 15, 89865023: 89865023
6 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh38 Chromosome 15, 89321792: 89321792
7 POLG NM_002693.2(POLG): c.2617G> T (p.Glu873Ter) single nucleotide variant Pathogenic rs121918047 GRCh37 Chromosome 15, 89864473: 89864473
8 POLG NM_002693.2(POLG): c.2617G> T (p.Glu873Ter) single nucleotide variant Pathogenic rs121918047 GRCh38 Chromosome 15, 89321242: 89321242
9 POLG POLG, TRP1020TER undetermined variant Pathogenic
10 POLG NM_002693.2(POLG): c.2209G> C (p.Gly737Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918054 GRCh37 Chromosome 15, 89866691: 89866691
11 POLG NM_002693.2(POLG): c.2209G> C (p.Gly737Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918054 GRCh38 Chromosome 15, 89323460: 89323460
12 POLG NM_002693.2(POLG): c.679C> T (p.Arg227Trp) single nucleotide variant Pathogenic rs121918056 GRCh37 Chromosome 15, 89873488: 89873488
13 POLG NM_002693.2(POLG): c.679C> T (p.Arg227Trp) single nucleotide variant Pathogenic rs121918056 GRCh38 Chromosome 15, 89330257: 89330257
14 POLG NM_002693.2(POLG): c.3218C> T (p.Pro1073Leu) single nucleotide variant Pathogenic rs267606959 GRCh37 Chromosome 15, 89862217: 89862217
15 POLG NM_002693.2(POLG): c.3218C> T (p.Pro1073Leu) single nucleotide variant Pathogenic rs267606959 GRCh38 Chromosome 15, 89318986: 89318986
16 POLG NM_002693.2(POLG): c.156_158delGCA (p.Gln55del) deletion Benign rs727504102 GRCh37 Chromosome 15, 89876828: 89876830
17 POLG NM_002693.2(POLG): c.156_158delGCA (p.Gln55del) deletion Benign rs727504102 GRCh38 Chromosome 15, 89333597: 89333599
18 POLG NM_002693.2(POLG): c.153_158delGCAGCA (p.Gln54_Gln55del) deletion Benign/Likely benign rs752180824 GRCh37 Chromosome 15, 89876828: 89876833
19 POLG NM_002693.2(POLG): c.153_158delGCAGCA (p.Gln54_Gln55del) deletion Benign/Likely benign rs752180824 GRCh38 Chromosome 15, 89333597: 89333602
20 POLG NM_002693.2(POLG): c.1837C> T (p.His613Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs147407423 GRCh37 Chromosome 15, 89868793: 89868793
21 POLG NM_002693.2(POLG): c.1837C> T (p.His613Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs147407423 GRCh38 Chromosome 15, 89325562: 89325562
22 POLG NM_002693.2(POLG): c.2369G> A (p.Arg790His) single nucleotide variant Uncertain significance rs191490663 GRCh37 Chromosome 15, 89866030: 89866030
23 POLG NM_002693.2(POLG): c.2369G> A (p.Arg790His) single nucleotide variant Uncertain significance rs191490663 GRCh38 Chromosome 15, 89322799: 89322799
24 POLG NM_002693.2(POLG): c.2724C> T (p.Ala908=) single nucleotide variant Conflicting interpretations of pathogenicity rs377390914 GRCh37 Chromosome 15, 89864366: 89864366
25 POLG NM_002693.2(POLG): c.2724C> T (p.Ala908=) single nucleotide variant Conflicting interpretations of pathogenicity rs377390914 GRCh38 Chromosome 15, 89321135: 89321135
26 POLG NM_002693.2(POLG): c.131A> G (p.Gln44Arg) single nucleotide variant Uncertain significance rs757120802 GRCh37 Chromosome 15, 89876855: 89876855
27 POLG NM_002693.2(POLG): c.131A> G (p.Gln44Arg) single nucleotide variant Uncertain significance rs757120802 GRCh38 Chromosome 15, 89333624: 89333624
28 POLG NM_002693.2(POLG): c.134A> G (p.Gln45Arg) single nucleotide variant Likely benign rs201016638 GRCh37 Chromosome 15, 89876852: 89876852
29 POLG NM_002693.2(POLG): c.134A> G (p.Gln45Arg) single nucleotide variant Likely benign rs201016638 GRCh38 Chromosome 15, 89333621: 89333621
30 POLG NM_002693.2(POLG): c.32G> A (p.Gly11Asp) single nucleotide variant Uncertain significance rs765472726 GRCh37 Chromosome 15, 89876954: 89876954
31 POLG NM_002693.2(POLG): c.32G> A (p.Gly11Asp) single nucleotide variant Uncertain significance rs765472726 GRCh38 Chromosome 15, 89333723: 89333723
32 POLG NM_002693.2(POLG): c.3176A> G (p.Asn1059Ser) single nucleotide variant Uncertain significance rs201192905 GRCh37 Chromosome 15, 89862259: 89862259
33 POLG NM_002693.2(POLG): c.3176A> G (p.Asn1059Ser) single nucleotide variant Uncertain significance rs201192905 GRCh38 Chromosome 15, 89319028: 89319028
34 POLG NM_002693.2(POLG): c.803G> C (p.Gly268Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs61752784 GRCh37 Chromosome 15, 89873364: 89873364
35 POLG NM_002693.2(POLG): c.803G> C (p.Gly268Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs61752784 GRCh38 Chromosome 15, 89330133: 89330133
36 POLG NM_002693.2(POLG): c.1174C> G (p.Leu392Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145289229 GRCh37 Chromosome 15, 89871763: 89871763
37 POLG NM_002693.2(POLG): c.1174C> G (p.Leu392Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145289229 GRCh38 Chromosome 15, 89328532: 89328532
38 POLG NM_002693.2(POLG): c.1586-5delC deletion Benign rs2307434 GRCh37 Chromosome 15, 89869974: 89869974
39 POLG NM_002693.2(POLG): c.1586-5delC deletion Benign rs2307434 GRCh38 Chromosome 15, 89326743: 89326743
40 POLG NM_002693.2(POLG): c.3559C> T (p.Arg1187Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs369544574 GRCh38 Chromosome 15, 89317460: 89317460
41 POLG NM_002693.2(POLG): c.3559C> T (p.Arg1187Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs369544574 GRCh37 Chromosome 15, 89860691: 89860691
42 POLG NM_002693.2(POLG): c.3346A> G (p.Met1116Val) single nucleotide variant Uncertain significance rs201144044 GRCh37 Chromosome 15, 89861908: 89861908
43 POLG NM_002693.2(POLG): c.3346A> G (p.Met1116Val) single nucleotide variant Uncertain significance rs201144044 GRCh38 Chromosome 15, 89318677: 89318677
44 POLG NM_002693.2(POLG): c.3323A> T (p.Tyr1108Phe) single nucleotide variant Uncertain significance rs765949668 GRCh37 Chromosome 15, 89861931: 89861931
45 POLG NM_002693.2(POLG): c.3323A> T (p.Tyr1108Phe) single nucleotide variant Uncertain significance rs765949668 GRCh38 Chromosome 15, 89318700: 89318700
46 POLG NM_002693.2(POLG): c.3287G> A (p.Arg1096His) single nucleotide variant Conflicting interpretations of pathogenicity rs368435864 GRCh37 Chromosome 15, 89861967: 89861967
47 POLG NM_002693.2(POLG): c.3287G> A (p.Arg1096His) single nucleotide variant Conflicting interpretations of pathogenicity rs368435864 GRCh38 Chromosome 15, 89318736: 89318736
48 POLG NM_002693.2(POLG): c.3286C> T (p.Arg1096Cys) single nucleotide variant Pathogenic rs201732356 GRCh37 Chromosome 15, 89861968: 89861968
49 POLG NM_002693.2(POLG): c.3286C> T (p.Arg1096Cys) single nucleotide variant Pathogenic rs201732356 GRCh38 Chromosome 15, 89318737: 89318737
50 POLG NM_002693.2(POLG): c.3286C> G (p.Arg1096Gly) single nucleotide variant Pathogenic/Likely pathogenic rs201732356 GRCh37 Chromosome 15, 89861968: 89861968

Expression for Mitochondrial Dna Depletion Syndrome 4a

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 4a.

Pathways for Mitochondrial Dna Depletion Syndrome 4a

Pathways related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.76 POLG2 TWNK

GO Terms for Mitochondrial Dna Depletion Syndrome 4a

Cellular components related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.55 DGUOK FARS2 POLG POLG2 TWNK
2 mitochondrial matrix GO:0005759 9.26 DGUOK FARS2 POLG2 TWNK
3 mitochondrial nucleoid GO:0042645 8.8 POLG POLG2 TWNK

Biological processes related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion organization GO:0007005 9.37 POLG2 TWNK
2 cellular response to glucose stimulus GO:0071333 9.32 POLG TWNK
3 DNA biosynthetic process GO:0071897 9.26 POLG POLG2
4 DNA-dependent DNA replication GO:0006261 9.16 POLG POLG2
5 DNA replication GO:0006260 9.13 POLG POLG2 TWNK
6 mitochondrial DNA replication GO:0006264 8.62 POLG TWNK

Molecular functions related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.56 DGUOK POLG POLG2 TYMP
2 protease binding GO:0002020 9.16 POLG TWNK
3 nucleotidyltransferase activity GO:0016779 8.96 POLG POLG2
4 DNA-directed DNA polymerase activity GO:0003887 8.62 POLG POLG2

Sources for Mitochondrial Dna Depletion Syndrome 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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