MTDPS7
MCID: MTC054
MIFTS: 51

Mitochondrial Dna Depletion Syndrome 7 (MTDPS7)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 7

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 7:

Name: Mitochondrial Dna Depletion Syndrome 7 56 12 73 29 13 6 15
Ohaha Syndrome 56 12 52 25 58 73
Iosca 56 52 25 58 73
Infantile Onset Spinocerebellar Ataxia 12 52 43 71
Infantile-Onset Spinocerebellar Ataxia 24 25 58 29
Ophthalmoplegia-Hypotonia-Ataxia-Hypoacusis-Athetosis Syndrome 52 58
Ophthalmoplegia, Hypotonia, Ataxia, Hypacusis, and Athetosis 52 25
Spinocerebellar Ataxia Infantile with Sensory Neuropathy 52 73
Spinocerebellar Ataxia 8 73 71
Mtdps7 56 73
Ophthalmoplegia, Hypotonia, Ataxia, Hypoacusis, and Athetosis 56
Ophthalmoplegia - Hypotonia - Ataxia - Hypoacusis - Athetosis 52
Spinocerebellar Ataxia, Infantile, with Sensory Neuropathy 56
Mitochondrial Dna Depletion Syndrome 7 Hepatocerebral Type 73
Ophthalmoplegia Hypotonia Ataxia Hypoacusis and Athetosis 73
Spinocerebellar Ataxia 8, Formerly; Sca8, Formerly 56
Spinocerebellar Ataxia, Infantile-Onset; Iosca 56
Mitochondrial Dna Depletion Syndrome , Type 7 39
Iosca, Mitochondrial Dna Depletion Syndrome 7 24
Pure Spinocerebellar Ataxia Japanese Type 73
Spinocerebellar Ataxia, Infantile-Onset 56
Spinocerebellar Ataxia Infantile-Onset 73
Spinocerebellar Ataxia 8, Formerly 56
Sca4 Pure Japanese Type 73
Sca8, Formerly 56
Sca8 73

Characteristics:

Orphanet epidemiological data:

58
infantile-onset spinocerebellar ataxia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: adolescent,early childhood,infantile,late childhood,young Adult;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset 6 to 18 months
some features occur in adolescence, including migraine, seizures, and psychiatric disorders
severe epilepsy may lead to early death
carrier frequency in finland is 1 in 230


HPO:

31
mitochondrial dna depletion syndrome 7:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0080126
OMIM 56 271245
OMIM Phenotypic Series 56 PS603041
MESH via Orphanet 44 C535523
ICD10 via Orphanet 33 G11.1
UMLS via Orphanet 72 C1849096
Orphanet 58 ORPHA1186
MedGen 41 C1849096
UMLS 71 C1837454 C1849096

Summaries for Mitochondrial Dna Depletion Syndrome 7

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1186 Definition Infantile-onset spinocerebellar ataxia (IOSCA) is a hereditary neurological disorder with early and severe involvement of both the peripheral and central nervous systems. It has only been described in Finnish families. Epidemiology So far, 24 cases have been reported. In Finland, IOSCA has a population carrier frequency of more than 1:230. Clinical description IOSCA is characterized by very early ataxia, athetosis and reduced tendon reflexes (between 9 and 18 months of age). Ophthalmoplegia and sensorineural hearing loss are diagnosed in childhood. Other features, such as optic atrophy and sensory neuropathy with progressive loss of myelinated fibers in the sural nerve, appear later in the disease course. Hypogonadism may occur in females. Some patients show intellectual deficit. Epilepsy is a late manifestation and seizures may be life-threatening. Etiology IOSCA is caused by mutations in the C10orf2 gene (10q24) encoding the mitochondrial helicase Twinkle. The c.1523A>G (p.Y508C) causative mutation has been postulated to be a founder mutation. Twenty-one of the reported patients were homozygous for this mutation, and three were compound heterozygotes : c.952G>A/c.1523A>G (two patients) and c.1523A>G/c.1287C>T (one patient). The mutations lead to mtDNA depletion in the brain and the liver, but not in the muscle. Diagnostic methods The diagnosis is based on clinical and pathological findings. Studies of sural nerve biopsies reveal an early and rapidly progressive axonal neuropathy. Neuroimaging studies revealing cerebellar atrophy and genetic testing for the c.1523A>G mutation may also help to confirm the diagnosis. Differential diagnosis Differential diagnoses include early-onset cerebellar ataxias with sensory axonal neuropathy and epileptic encephalopathy , mitochondrial disorders with axonal neuropathy (such as Friedreich ataxia), progressive external ophthalmoplegia (PEO), juvenile- or adult-onset mitochondrial recessive ataxia syndrome (MIRAS), and POLG -related disorders (see theseterms). Antenatal diagnosis Prenatal testing may be available for families in which the disease-causing mutations have already been identified. Genetic counseling IOSCA is inherited in an autosomal recessive manner. Genetic counseling is an important clinical tool for preventing new cases, especially for couples with an affected first child: the risk of having an affected child in further pregnancies is 25%. Management and treatment IOSCA patients are often managed by a multidisciplinary team, involving a pediatrician , neurologist , psychiatrist , orthopedic surgeon, physical and occupational therapists , genetic counselor, and social worker. Treatment is symptomatic and may include: (1) hearing aids, speech therapy and sign language for deafness; (2) physical therapy , orthotic devices and orthopedic surgery for sensory axonal neuropathy; (3) walking aids, a wheelchair, physiotherapy and occupational therapy for ataxia; (4) antiepileptic drugs for seizures and (5) antipsychotics and antidepressants for psychiatric symptoms. Prognosis Prognosis is unfavorable. Patients are wheelchair-bound by adolescence. Early death is common due to severe seizures. The clinical course seems to be more rapid and severe (with death during infancy) in c.952G>A/ c.1523A>G compound heterozygotes. Visit the Orphanet disease page for more resources.

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 7, also known as ohaha syndrome, is related to polyneuropathy and friedreich ataxia, and has symptoms including muscle weakness, ataxia and tremor. An important gene associated with Mitochondrial Dna Depletion Syndrome 7 is TWNK (Twinkle MtDNA Helicase), and among its related pathways/superpathways are Mitochondrial Gene Expression and Nucleotide Metabolism. Affiliated tissues include brain, liver and eye, and related phenotypes are hearing impairment and optic atrophy

Disease Ontology : 12 A mitochondrial DNA depletion syndrome that is characterized by progressive ataxia, hypotonia, hyporeflexia, athetosis and sensory impairment and has material basis in autosomal recessive homozygous or compound heterozygous mutation in the C10ORF2 gene, which encodes the twinkle and twinky proteins, on chromosome 10q24.

Genetics Home Reference : 25 Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance. People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation. IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness. Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy). Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5.

OMIM : 56 Mitochondrial DNA depletion syndrome-7 is an autosomal recessive severe neurodegenerative disorder characterized primarily by hypotonia, ataxia, ophthalmoplegia, hearing loss, seizures, and sensory axonal neuropathy. Although originally classified as a form of spinocerebellar ataxia (see, e.g., SCA1, 164400) (Koskinen et al., 1994), it has been reclassified as a mitochondrial DNA depletion syndrome (Hakonen et al., 2008) based on the finding of mtDNA depletion in the brain and liver of affected individuals. For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (271245)

UniProtKB/Swiss-Prot : 73 Mitochondrial DNA depletion syndrome 7: A severe disease associated with mitochondrial dysfunction. Some patients are affected by progressive atrophy of the cerebellum, brain stem, the spinal cord, and sensory axonal neuropathy. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. In some individuals liver dysfunction and multi-organ failure is present.

GeneReviews: NBK3795

Related Diseases for Mitochondrial Dna Depletion Syndrome 7

Diseases in the Mitochondrial Dna Depletion Syndrome family:

Mitochondrial Dna Depletion Syndrome 4a Mitochondrial Dna Depletion Syndrome 9
Mitochondrial Dna Depletion Syndrome 3 Mitochondrial Dna Depletion Syndrome 6
Mitochondrial Dna Depletion Syndrome 7 Mitochondrial Dna Depletion Syndrome 1
Mitochondrial Dna Depletion Syndrome 2 Mitochondrial Dna Depletion Syndrome 5
Mitochondrial Dna Depletion Syndrome 8a Mitochondrial Dna Depletion Syndrome 4b
Mitochondrial Dna Depletion Syndrome 11 Mitochondrial Dna Depletion Syndrome 12b , Autosomal Recessive
Mitochondrial Dna Depletion Syndrome 13 Mitochondrial Dna Depletion Syndrome 14
Mitochondrial Dna Depletion Syndrome 15 Mitochondrial Dna Depletion Syndrome 12a , Autosomal Dominant
Mitochondrial Dna Depletion Syndrome 16 Mitochondrial Dna Depletion Syndrome 17
Mitochondrial Dna Depletion Syndrome 18 Mitochondrial Dna Depletion Syndrome 12a
Mitochondrial Dna Depletion Syndrome 12b Mitochondrial Dna Deletion Syndromes
Multiple Mitochondrial Dna Deletion Syndrome

Diseases related to Mitochondrial Dna Depletion Syndrome 7 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 123)
# Related Disease Score Top Affiliating Genes
1 polyneuropathy 30.0 TWNK POLG MPV17
2 friedreich ataxia 29.9 POLG FXN APTX
3 axonal neuropathy 29.8 TWNK SLC25A4 RRM2B POLG2 POLG MPV17
4 hereditary ataxia 29.3 TWNK SACS FXN APTX
5 autosomal dominant progressive external ophthalmoplegia 29.3 TWNK SLC25A4 RRM2B POLG2 POLG DNA2
6 autosomal dominant cerebellar ataxia 29.3 TWNK SACS POLG FXN APTX
7 peripheral nervous system disease 28.6 TYMP TWNK SACS POLG FXN APTX
8 myopathy 28.4 TYMP TWNK SLC25A4 RRM2B POLG2 POLG
9 chronic progressive external ophthalmoplegia 27.2 TYMP TWNK SSBP1 SLC25A4 RRM2B POLG2
10 3-methylglutaconic aciduria, type iii 27.0 TYMP TWNK SUCLG1 SLC25A4 POLG2 POLG
11 kearns-sayre syndrome 26.2 TYMP TWNK SUCLG1 SSBP1 SLC25A4 RRM2B
12 spinocerebellar ataxia 8 12.8
13 spinocerebellar ataxia, autosomal recessive 8 11.7
14 spinocerebellar ataxia 31 11.6
15 spinocerebellar ataxia 12 11.6
16 spinocerebellar ataxia, autosomal recessive 14 11.5
17 anemia, sideroblastic, and spinocerebellar ataxia 11.4
18 ataxia neuropathy spectrum 10.4 TWNK POLG
19 machado-joseph disease 10.4
20 dentatorubral-pallidoluysian atrophy 10.4
21 polg-related disorders 10.4 TWNK POLG
22 parkinson disease, late-onset 10.4
23 branchiootic syndrome 1 10.3
24 status epilepticus 10.3
25 spinocerebellar ataxia 4 10.3
26 hypogonadism 10.3
27 sensory peripheral neuropathy 10.3
28 neuropathy 10.3
29 visual cortex disease 10.3 POLG2 POLG
30 mitochondrial dna depletion syndrome, encephalomyopathic form 10.3 SUCLG1 RRM2B
31 coenzyme q10 deficiency disease 10.2 POLG APTX
32 spinocerebellar ataxia 2 10.2
33 spinocerebellar ataxia 5 10.2
34 alacrima, achalasia, and mental retardation syndrome 10.2
35 pathologic nystagmus 10.2
36 visual pathway disease 10.2 POLG2 POLG
37 mitochondrial dna depletion syndrome 12a 10.2 SLC25A4 POLG
38 ataxia and polyneuropathy, adult-onset 10.2
39 athetosis 10.2
40 hypotonia 10.2
41 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 10.2 POLG MPV17
42 chorea, childhood-onset, with psychomotor retardation 10.2
43 choreatic disease 10.2
44 dystonia 10.2
45 spinocerebellar atrophy 10.2
46 spastic paraplegia 7, autosomal recessive 10.1 SACS APTX
47 myotonic cataract 10.1 TYMP TWNK POLG
48 spinocerebellar ataxia 29 10.1
49 seizures, benign familial neonatal, 1 10.1
50 spinocerebellar ataxia 1 10.1

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 7:



Diseases related to Mitochondrial Dna Depletion Syndrome 7

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 7

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 7:

58 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000365
2 optic atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000648
3 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
4 reduced tendon reflexes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001315
5 ophthalmoplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000602
6 abnormality of the autonomic nervous system 58 31 hallmark (90%) Very frequent (99-80%) HP:0002270
7 elevated hepatic transaminase 31 occasional (7.5%) HP:0002910
8 intellectual disability 31 HP:0001249
9 muscular hypotonia 31 HP:0001252
10 muscle weakness 31 HP:0001324
11 nystagmus 31 HP:0000639
12 abnormality of movement 58 Very frequent (99-80%)
13 specific learning disability 31 HP:0001328
14 cerebral cortical atrophy 31 HP:0002120
15 areflexia 31 HP:0001284
16 migraine 31 HP:0002076
17 psychosis 31 HP:0000709
18 cerebellar atrophy 31 HP:0001272
19 poor eye contact 31 HP:0000817
20 encephalopathy 31 HP:0001298
21 clumsiness 31 HP:0002312
22 status epilepticus 31 HP:0002133
23 hypergonadotropic hypogonadism 31 HP:0000815
24 athetosis 31 HP:0002305
25 loss of ability to walk 31 HP:0006957
26 generalized hypotonia 31 HP:0001290
27 excessive daytime somnolence 31 HP:0001262
28 atrophy/degeneration affecting the brainstem 31 HP:0007366
29 epileptic encephalopathy 31 HP:0200134
30 sensory axonal neuropathy 31 HP:0003390
31 epilepsia partialis continua 31 HP:0012847

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
optic atrophy
nystagmus
ophthalmoplegia
poor eye contact
abnormal eye movements

Neurologic Central Nervous System:
ataxia
cerebellar atrophy
clumsiness
status epilepticus
athetosis
more
Neurologic Peripheral Nervous System:
sensory axonal neuropathy
loss of deep tendon reflexes

Abdomen Liver:
mitochondrial dna depletion

Endocrine Features:
hypergonadotrophic hypogonadism (in females in adolescence)

Muscle Soft Tissue:
muscle weakness
hypotonia
decreased complex i activity (rare)

Neurologic Behavioral Psychiatric Manifestations:
psychosis
somnolence
mood disorders
uncontrolled rage

Head And Neck Ears:
deafness
loss of vestibular caloric response

Genitourinary Internal Genitalia Female:
hypergonadotrophic hypogonadism (in females in adolescence)

Laboratory Abnormalities:
abnormal liver enzymes (rare)

Clinical features from OMIM:

271245

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 7:


muscle weakness, ataxia, tremor, ophthalmoplegia, clumsiness, athetosis, muscle spasticity, abnormal pyramidal signs

MGI Mouse Phenotypes related to Mitochondrial Dna Depletion Syndrome 7:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.36 APTX DNA2 FXN MGME1 MPV17 POLG

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 7

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 7

Cochrane evidence based reviews: infantile onset spinocerebellar ataxia

Genetic Tests for Mitochondrial Dna Depletion Syndrome 7

Genetic tests related to Mitochondrial Dna Depletion Syndrome 7:

# Genetic test Affiliating Genes
1 Mitochondrial Dna Depletion Syndrome 7 (hepatocerebral Type) 29 TWNK
2 Infantile-Onset Spinocerebellar Ataxia 29

Anatomical Context for Mitochondrial Dna Depletion Syndrome 7

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 7:

40
Brain, Liver, Eye, Cerebellum, Spinal Cord, Testes

Publications for Mitochondrial Dna Depletion Syndrome 7

Articles related to Mitochondrial Dna Depletion Syndrome 7:

(show all 33)
# Title Authors PMID Year
1
Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion. 24 56 6
17722119 2007
2
Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. 24 6 56
17921179 2007
3
Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. 24 6 56
16135556 2005
4
Recessive twinkle mutations cause severe epileptic encephalopathy. 24 56
19304794 2009
5
Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion. 56 24
18775955 2008
6
Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease. 56 24
8133312 1994
7
Mitochondrial DNA Maintenance Defects Overview 6
29517884 2018
8
Infantile-Onset Spinocerebellar Ataxia 6
20301746 2009
9
cDNA cloning, expression profile and genomic structure of a novel human transcript on chromosome 10q24, and its analyses as a candidate gene for infantile onset spinocerebellar ataxia. 56
12459258 2002
10
Toward cloning of a novel ataxia gene: refined assignment and physical map of the IOSCA locus (SCA8) on 10q24. 56
9027505 1997
11
Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus. 56
7726163 1995
12
Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease. 24
27551684 2016
13
Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy. 24
24816431 2014
14
Exome sequencing reveals a homozygous mutation in TWINKLE as the cause of multisystemic failure including renal tubulopathy in three siblings. 24
23375728 2013
15
Physiological and biochemical defects in carboxyl-terminal mutants of mitochondrial DNA helicase. 24
18593709 2008
16
Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro. 24
18685103 2008
17
Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia. 24
18279890 2008
18
The N-terminal domain of TWINKLE contributes to single-stranded DNA binding and DNA helicase activities. 24
18039713 2008
19
Twinkle, the mitochondrial replicative DNA helicase, is widespread in the eukaryotic radiation and may also be the mitochondrial DNA primase in most eukaryotes. 24
16612544 2006
20
Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number. 24
15509589 2004
21
Reconstitution of a minimal mtDNA replisome in vitro. 24
15167897 2004
22
TWINKLE Has 5' -> 3' DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. 24
12975372 2003
23
Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. 24
11431692 2001
24
Infantile onset spinocerebellar ataxia with sensory neuropathy (IOSCA): neuropathological features. 24
9879682 1998
25
Primary hypogonadism in females with infantile onset spinocerebellar ataxia. 24
8552218 1995
26
Infantile-onset spinocerebellar ataxia: MR and CT findings. 24
7484627 1995
27
Sensory neuropathy in infantile onset spinocerebellar ataxia (IOSCA). 24
8159181 1994
28
Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. 24
1634620 1992
29
An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. 24
2725645 1989
30
Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report. 61
32234020 2020
31
Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy. 61
31823625 2019
32
Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features. 61
25355836 2014
33
Bovine TWINKLE and mitochondrial ribosomal protein L43 genes are regulated by an evolutionary conserved bidirectional promoter. 61
24361965 2014

Variations for Mitochondrial Dna Depletion Syndrome 7

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:

6 (show top 50) (show all 85) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TWNK NM_021830.5(TWNK):c.49del (p.Leu17fs)deletion Pathogenic 694436 10:102748013-102748013 10:100988256-100988256
2 TWNK NM_021830.5(TWNK):c.1370C>T (p.Thr457Ile)SNV Pathogenic 4626 rs80356544 10:102749527-102749527 10:100989770-100989770
3 TWNK NM_021830.5(TWNK):c.1523A>G (p.Tyr508Cys)SNV Pathogenic 4627 rs80356540 10:102750231-102750231 10:100990474-100990474
4 TWNK NM_021830.5(TWNK):c.952G>A (p.Ala318Thr)SNV Pathogenic 4630 rs80356542 10:102748919-102748919 10:100989162-100989162
5 TWNK NM_021830.5(TWNK):c.1287C>T (p.Ala429=)SNV Pathogenic 21673 rs80356541 10:102749444-102749444 10:100989687-100989687
6 TWNK NM_021830.5(TWNK):c.333del (p.Leu112fs)deletion Pathogenic 225837 rs886037832 10:102748298-102748298 10:100988541-100988541
7 TWNK NM_021830.5(TWNK):c.904C>T (p.Arg302Trp)SNV Likely pathogenic 225838 rs374997012 10:102748871-102748871 10:100989114-100989114
8 TWNK NM_021830.5(TWNK):c.1387C>T (p.Arg463Trp)SNV Likely pathogenic 56727 rs386834146 10:102749544-102749544 10:100989787-100989787
9 TWNK NM_021830.5(TWNK):c.1199G>T (p.Arg400Leu)SNV Likely pathogenic 694431 10:102749166-102749166 10:100989409-100989409
10 TWNK NM_021830.5(TWNK):c.1314C>G (p.Asn438Lys)SNV Likely pathogenic 694434 10:102749471-102749471 10:100989714-100989714
11 TWNK NM_021830.5(TWNK):c.1628G>A (p.Arg543Gln)SNV Likely pathogenic 694432 10:102750661-102750661 10:100990904-100990904
12 TWNK NM_021830.5(TWNK):c.1441C>G (p.Leu481Val)SNV Likely pathogenic 638300 10:102749598-102749598 10:100989841-100989841
13 TWNK NM_021830.5(TWNK):c.56G>A (p.Gly19Glu)SNV Conflicting interpretations of pathogenicity 426493 rs767175342 10:102748023-102748023 10:100988266-100988266
14 TWNK NM_021830.5(TWNK):c.1244-14C>TSNV Conflicting interpretations of pathogenicity 507889 rs758757135 10:102749387-102749387 10:100989630-100989630
15 TWNK NM_021830.5(TWNK):c.1070G>C (p.Arg357Pro)SNV Conflicting interpretations of pathogenicity 632124 rs758026634 10:102749037-102749037 10:100989280-100989280
16 TWNK NM_021830.5(TWNK):c.672T>C (p.Ala224=)SNV Conflicting interpretations of pathogenicity 878844 10:102748639-102748639 10:100988882-100988882
17 TWNK NM_021830.5(TWNK):c.639C>T (p.Gly213=)SNV Conflicting interpretations of pathogenicity 136587 rs11542130 10:102748606-102748606 10:100988849-100988849
18 TWNK NM_021830.5(TWNK):c.1953G>A (p.Lys651=)SNV Conflicting interpretations of pathogenicity 878401 10:102753165-102753165 10:100993408-100993408
19 TWNK NM_021830.5(TWNK):c.1735-14C>ASNV Conflicting interpretations of pathogenicity 136594 rs201795189 10:102752933-102752933 10:100993176-100993176
20 TWNK NM_021830.5(TWNK):c.1196A>G (p.Asn399Ser)SNV Conflicting interpretations of pathogenicity 214185 rs863223921 10:102749163-102749163 10:100989406-100989406
21 TWNK NM_021830.5(TWNK):c.1697A>G (p.Lys566Arg)SNV Conflicting interpretations of pathogenicity 214177 rs116046810 10:102750730-102750730 10:100990973-100990973
22 TWNK NM_021830.5(TWNK):c.1975G>A (p.Ala659Thr)SNV Conflicting interpretations of pathogenicity 214178 rs370814108 10:102753187-102753187 10:100993430-100993430
23 TWNK NM_021830.5(TWNK):c.2045G>A (p.Arg682His)SNV Conflicting interpretations of pathogenicity 214180 rs182559752 10:102753257-102753257 10:100993500-100993500
24 TWNK NM_021830.5(TWNK):c.241C>G (p.Leu81Val)SNV Conflicting interpretations of pathogenicity 279715 rs145068570 10:102748208-102748208 10:100988451-100988451
25 TWNK NM_021830.5(TWNK):c.384C>T (p.Ser128=)SNV Conflicting interpretations of pathogenicity 281415 rs148234280 10:102748351-102748351 10:100988594-100988594
26 TWNK NM_021830.5(TWNK):c.-650A>GSNV Conflicting interpretations of pathogenicity 298484 rs187213541 10:102747318-102747318 10:100987561-100987561
27 TWNK NM_021830.5(TWNK):c.1042G>A (p.Gly348Arg)SNV Conflicting interpretations of pathogenicity 298500 rs62626271 10:102749009-102749009 10:100989252-100989252
28 TWNK NM_021830.5(TWNK):c.1488T>C (p.Thr496=)SNV Conflicting interpretations of pathogenicity 298502 rs549767223 10:102750196-102750196 10:100990439-100990439
29 TWNK NM_021830.5(TWNK):c.-290G>CSNV Conflicting interpretations of pathogenicity 298491 rs62626270 10:102747678-102747678 10:100987921-100987921
30 TWNK NM_021830.5(TWNK):c.*301C>TSNV Conflicting interpretations of pathogenicity 298507 rs41291468 10:102753568-102753568 10:100993811-100993811
31 TWNK NM_021830.5(TWNK):c.492C>T (p.Leu164=)SNV Conflicting interpretations of pathogenicity 298498 rs775463083 10:102748459-102748459 10:100988702-100988702
32 TWNK NM_021830.5(TWNK):c.922T>C (p.Leu308=)SNV Conflicting interpretations of pathogenicity 298499 rs754389465 10:102748889-102748889 10:100989132-100989132
33 TWNK NM_021830.5(TWNK):c.1101C>T (p.Ile367=)SNV Conflicting interpretations of pathogenicity 298501 rs200798080 10:102749068-102749068 10:100989311-100989311
34 TWNK NM_021830.5(TWNK):c.76G>A (p.Gly26Ser)SNV Conflicting interpretations of pathogenicity 298494 rs577209883 10:102748043-102748043 10:100988286-100988286
35 TWNK NM_021830.5(TWNK):c.*419A>TSNV Conflicting interpretations of pathogenicity 298509 rs187553791 10:102753686-102753686 10:100993929-100993929
36 TWNK NM_021830.5(TWNK):c.1609T>C (p.Tyr537His)SNV Conflicting interpretations of pathogenicity 383137 rs144001072 10:102750642-102750642 10:100990885-100990885
37 TWNK NM_021830.5(TWNK):c.1853C>T (p.Pro618Leu)SNV Uncertain significance 298504 rs886046632 10:102753065-102753065 10:100993308-100993308
38 TWNK NM_021830.5(TWNK):c.*574C>TSNV Uncertain significance 298515 rs886046636 10:102753841-102753841 10:100994084-100994084
39 TWNK NM_021830.5(TWNK):c.*619G>ASNV Uncertain significance 298516 rs886046637 10:102753886-102753886 10:100994129-100994129
40 TWNK NM_021830.5(TWNK):c.*709C>GSNV Uncertain significance 298517 rs41291470 10:102753976-102753976 10:100994219-100994219
41 TWNK NM_021830.5(TWNK):c.*747C>GSNV Uncertain significance 298518 rs886046638 10:102754014-102754014 10:100994257-100994257
42 TWNK NM_021830.5(TWNK):c.*763T>CSNV Uncertain significance 298519 rs886046639 10:102754030-102754030 10:100994273-100994273
43 TWNK NM_021830.5(TWNK):c.-585T>GSNV Uncertain significance 298486 rs886046624 10:102747383-102747383 10:100987626-100987626
44 TWNK NM_021830.5(TWNK):c.77G>T (p.Gly26Val)SNV Uncertain significance 298495 rs772221026 10:102748044-102748044 10:100988287-100988287
45 TWNK NM_021830.5(TWNK):c.*438G>CSNV Uncertain significance 298510 rs886046634 10:102753705-102753705 10:100993948-100993948
46 TWNK NM_021830.5(TWNK):c.-549G>ASNV Uncertain significance 298487 rs886046625 10:102747419-102747419 10:100987662-100987662
47 TWNK NM_021830.5(TWNK):c.-470G>ASNV Uncertain significance 298488 rs886046626 10:102747498-102747498 10:100987741-100987741
48 TWNK NM_021830.5(TWNK):c.*555G>ASNV Uncertain significance 298514 rs886046635 10:102753822-102753822 10:100994065-100994065
49 TWNK NM_021830.5(TWNK):c.276C>T (p.Gly92=)SNV Uncertain significance 298497 rs886046631 10:102748243-102748243 10:100988486-100988486
50 TWNK NM_021830.5(TWNK):c.-644A>TSNV Uncertain significance 298485 rs886046623 10:102747324-102747324 10:100987567-100987567

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:

73
# Symbol AA change Variation ID SNP ID
1 TWNK p.Thr457Ile VAR_039045 rs80356544
2 TWNK p.Tyr508Cys VAR_043797 rs80356540
3 TWNK p.Ala318Thr VAR_065104 rs80356542
4 TWNK p.Leu360Gly VAR_065107
5 TWNK p.Leu456Val VAR_067722 rs386834145

Expression for Mitochondrial Dna Depletion Syndrome 7

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 7.

Pathways for Mitochondrial Dna Depletion Syndrome 7

GO Terms for Mitochondrial Dna Depletion Syndrome 7

Cellular components related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.73 TWNK SUCLG1 SSBP1 POLG2 FXN DGUOK
2 mitochondrion GO:0005739 9.5 TWNK SUCLG1 SSBP1 SLC25A4 SACS RRM2B
3 mitochondrial nucleoid GO:0042645 9.35 TWNK SSBP1 POLG2 POLG DNA2
4 gamma DNA polymerase complex GO:0005760 9.33 POLG2 POLG DNA2

Biological processes related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.77 RRM2B POLG2 MGME1 DNA2 APTX
2 DNA replication GO:0006260 9.63 TWNK SSBP1 RRM2B POLG2 POLG DNA2
3 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.62 POLG MGME1 DNA2 APTX
4 mitochondrion organization GO:0007005 9.56 TWNK SSBP1 POLG2 FXN
5 DNA-dependent DNA replication GO:0006261 9.48 POLG2 POLG
6 mitochondrion morphogenesis GO:0070584 9.46 SSBP1 POLG2
7 DNA unwinding involved in DNA replication GO:0006268 9.43 TWNK SSBP1
8 mitochondrial DNA repair GO:0043504 9.4 MGME1 DNA2
9 mitochondrial genome maintenance GO:0000002 9.26 TYMP SLC25A4 MPV17 MGME1
10 mitochondrial DNA replication GO:0006264 9.17 TWNK SSBP1 RRM2B POLG2 POLG MGME1

Molecular functions related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-directed DNA polymerase activity GO:0003887 9.16 POLG2 POLG
2 single-stranded DNA binding GO:0003697 9.13 TWNK SSBP1 APTX
3 5'-3' DNA helicase activity GO:0043139 8.62 TWNK DNA2

Sources for Mitochondrial Dna Depletion Syndrome 7

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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68 SNOMED-CT via HPO
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