Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

PEOA4 MCID: PRG040 MIFTS: 54	Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 (PEOA4) Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs Expand all tables

Sources

Aliases & Classifications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

MalaCards integrated aliases for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Name: Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 ⁵⁶ ¹³

Autosomal Dominant Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 4 ¹² ²⁹ ⁶ ¹⁵

Peoa4 ⁵⁶ ¹² ⁷³

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant, 4 ⁷³ ⁷¹

Chronic Progressive External Ophthalmoplegia ⁷³ ⁷¹

Ophthalmoplegia, External, Progressive, with Mitochondrial Dna Deletions, Autosomal Dominant, Type 4 ³⁹

Progressive External Ophthalmoplegia, Autosomal Dominant 4 ⁵⁶

Autosomal Dominant Progressive External Ophthalmoplegia 4 ¹²

Progressive External Ophthalmoplegia Autosomal Dominant 4 ⁷³

Ocular Myopathy of Von Graefe-Fuchs ⁷³

Mitochondrial Ocular Myopathy ⁷³

Kearns-Sayre Syndrome ⁷¹

Graefe Disease ⁷³

Cpeo ⁷³

Characteristics:

OMIM:

⁵⁶

Inheritance:
autosomal dominant

Miscellaneous:
variable severity
progressive disorder
variable age at onset (range infancy to adult)

HPO:

³¹

progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 4:
Inheritance autosomal dominant inheritance
Onset and clinical course variable expressivity progressive adult onset

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases Fetal diseases
Anatomical: Muscle diseases Neuronal diseases Bone diseases Eye diseases Ear diseases Cardiovascular diseases

See all MalaCards categories (disease lists)

External Ids:

Disease Ontology ¹² DOID:0111525

OMIM ⁵⁶ 610131

OMIM Phenotypic Series ⁵⁶ PS157640

MeSH ⁴³ D017246

MedGen ⁴¹ C1864668

UMLS ⁷¹ C0022541 C0162674 C1864668

Sources

Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

UniProtKB/Swiss-Prot : ⁷³ Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 4: A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.

MalaCards based summary : Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4, also known as autosomal dominant progressive external ophthalmoplegia with mitochondrial dna deletions 4, is related to chronic progressive external ophthalmoplegia and kearns-sayre syndrome, and has symptoms including seizures, muscle weakness and myalgia. An important gene associated with Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 is POLG2 (DNA Polymerase Gamma 2, Accessory Subunit), and among its related pathways/superpathways are Mitochondrial Gene Expression and Propanoate metabolism. The drugs Coenzyme Q10 and Ubiquinone have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, liver and eye, and related phenotypes are global developmental delay and gastroesophageal reflux

Disease Ontology : ¹² A chronic progressive external ophthalmoplegia that has material basis in heterozygous mutation in POLG2 on chromosome 17q23.3.

OMIM : ⁵⁶ Progressive external ophthalmoplegia-4 is an autosomal dominant form of mitochondrial disease that variably affects skeletal muscle, the nervous system, the liver, and the gastrointestinal tract. Age at onset ranges from infancy to adulthood. The phenotype ranges from relatively mild, with adult-onset skeletal muscle weakness and weakness of the external eye muscles, to severe, with a multisystem disorder characterized by delayed psychomotor development, lactic acidosis, constipation, and liver involvement (summary by Young et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640). (610131)

Sources

Related Diseases for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Diseases in the Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1 family:

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 1	Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 3	Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 5	Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 2	Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 3
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4	Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 5

Diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 151)

#	Related Disease	Score	Top Affiliating Genes
1	chronic progressive external ophthalmoplegia	32.5	TYMP TWNK SSBP1 SLC25A4 RRM2B POLG2
2	kearns-sayre syndrome	30.6	TYMP TWNK SUCLG1 SSBP1 SLC25A4 RRM2B
3	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1	30.4	TYMP TWNK SUCLG1 SUCLA2 SSBP1 SLC25A4
4	sensory ataxic neuropathy, dysarthria, and ophthalmoparesis	30.2	TYMP TWNK SUCLG1 SSBP1 SLC25A4 RRM2B
5	ptosis	30.1	TYMP TWNK SLC25A4 RRM2B POLG2 POLG
6	mitochondrial disorders	30.1	TWNK SLC25A4 RRM2B POLG DGUOK
7	mitochondrial neurogastrointestinal encephalomyopathy	30.0	TYMP RRM2B POLG
8	polyneuropathy	29.6	TWNK POLG MPV17
9	optic nerve disease	29.4	TWNK POLG MT-ND2 IMMT
10	autosomal dominant progressive external ophthalmoplegia	29.2	TWNK SLC25A4 RRM2B POLG2 POLG
11	myopathy	29.2	TYMP TWNK SLC25A4 RRM2B POLG2 POLG
12	mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes	29.1	TYMP TWNK POLG MT-ND2 DGUOK
13	mitochondrial encephalomyopathy	28.7	TYMP TWNK SUCLG1 SUCLA2 POLG MT-ND2
14	mitochondrial myopathy	28.0	TYMP TWNK SUCLG1 SSBP1 SLC25A4 RRM2B
15	3-methylglutaconic aciduria, type iii	27.7	TYMP TWNK SUCLG1 SUCLA2 SLC25A4 POLG2
16	leber optic atrophy	27.6	TYMP TWNK SLC25A4 RRM2B POLG2 POLG
17	leigh syndrome	27.5	TYMP TWNK SUCLG1 POLG2 POLG MT-ND2
18	mitochondrial metabolism disease	26.7	TYMP TWNK SUCLG1 SUCLA2 SSBP1 SLC25A4
19	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 2	12.4
20	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 1	12.2
21	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3	12.2
22	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2	12.2
23	ocular muscular dystrophy	11.9
24	mitochondrial dna-related progressive external ophthalmoplegia	11.9
25	strabismus	11.7
26	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 5	11.4
27	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 6	11.4
28	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 3	11.4
29	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 4	11.4
30	progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 5	11.4
31	dysphagia	10.5
32	mechanical strabismus	10.4
33	branchiootic syndrome 1	10.4
34	neuropathy	10.4
35	lactic acidosis	10.3
36	myasthenia gravis	10.3
37	retinitis pigmentosa	10.3
38	ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus	10.3
39	neuroretinitis	10.3
40	alternating exotropia	10.3
41	exotropia	10.3
42	retinitis	10.3
43	encephalopathy	10.3
44	hereditary optic neuropathy	10.3
45	mitochondrial dna depletion syndrome 8a	10.2	TYMP RRM2B
46	ataxia and polyneuropathy, adult-onset	10.2
47	lagophthalmos	10.2
48	peripheral nervous system disease	10.2
49	mitochondrial dna depletion syndrome 1	10.2	TYMP POLG
50	visual cortex disease	10.2	POLG2 POLG

Graphical network of the top 20 diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4

Sources

Symptoms & Phenotypes for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Human phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

³¹ (show all 23)

#	Description	HPO Frequency	HPO Source Accession
1	global developmental delay ³¹	occasional (7.5%)	HP:0001263
2	gastroesophageal reflux ³¹	occasional (7.5%)	HP:0002020
3	failure to thrive ³¹	occasional (7.5%)	HP:0001508
4	elevated hepatic transaminase ³¹	occasional (7.5%)	HP:0002910
5	constipation ³¹	occasional (7.5%)	HP:0002019
6	cerebellar atrophy ³¹	occasional (7.5%)	HP:0001272
7	generalized hypotonia ³¹	occasional (7.5%)	HP:0001290
8	gastroparesis ³¹	occasional (7.5%)	HP:0002578
9	cerebral visual impairment ³¹	occasional (7.5%)	HP:0100704
10	seizure ³¹	occasional (7.5%)	HP:0001250
11	elevated serum creatine kinase ³¹		HP:0003236
12	arrhythmia ³¹		HP:0011675
13	myalgia ³¹		HP:0003326
14	ptosis ³¹		HP:0000508
15	progressive external ophthalmoplegia ³¹		HP:0000590
16	facial palsy ³¹		HP:0010628
17	increased serum lactate ³¹		HP:0002151
18	progressive muscle weakness ³¹		HP:0003323
19	limb muscle weakness ³¹		HP:0003690
20	exercise intolerance ³¹		HP:0003546
21	cytochrome c oxidase-negative muscle fibers ³¹		HP:0003688
22	impaired glucose tolerance ³¹		HP:0040270
23	multiple mitochondrial dna deletions ³¹		HP:0003689

Symptoms via clinical synopsis from OMIM:

⁵⁶

Head And Neck Eyes:
ptosis
external ophthalmoplegia, progressive (peo)
cortical blindness (1 patient)

Muscle Soft Tissue:
limb muscle weakness
exercise intolerance
muscle pain
facial muscle weakness
muscle weakness, progressive
more

Cardiovascular Heart:
cardiac conduction defects

Growth Other:
failure to thrive (in some patients)

Abdomen Liver:
liver disease (in some patients)

Laboratory Abnormalities:
increased serum lactate
increased serum creatine kinase
abnormal liver enzymes (in some patients)

Endocrine Features:
impaired glucose tolerance

Neurologic Central Nervous System:
seizures (in some patients)
developmental delay (in some patients)
hypotonia (in some patients)
cerebellar atrophy (1 patient)

Abdomen Gastrointestinal:
gastroesophageal reflux (in some patients)
constipation (in some patients)
delayed gastric emptying (in some patients)

Clinical features from OMIM:

610131

UMLS symptoms related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

seizures, muscle weakness, myalgia, ophthalmoplegia, cerebellar ataxia, facial paresis

MGI Mouse Phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	cellular	MP:0005384	9.7	FASLG MPV17 MT-ND2 POLG POLG2 RRM2B
2	mortality/aging	MP:0010768	9.36	FASLG INTS2 MPV17 POLG POLG2 RRM2B

Sources

Drugs & Therapeutics for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Drugs for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

Name

Status

Phase

Clinical Trials

Cas Number

PubChem Id

Coenzyme Q10

Approved, Investigational, Nutraceutical

303-98-0

5281915

Synonyms:

(all-e)-2-(3,7,11,15,19,23,27,31,35,39-Decamethyl-2,6,10,14,18,22,26,30,34,38-tetracontadecaenyl)-5,6-dimethoxy-3-methyl-2,5-cyclohexadiene-1,4-dione

(all-e)-2,3-Dimethoxy-5-methyl-6-(3,7,11,15,19,23,27,31-octamethyl-2,6,10,14,18,22,26,30-dotriacontaoctaenyl)-2,5-cyclohexadiene-1,4-dione

2-((all-e)-3,7,11,15,19,23,27,31,35,39-Decamethyl-2,6,10,14,18,22,26,30,34,38-tetracontadecaenyl)-5,6-dimethoxy-3-methyl-P-benzoquinone

2-(3,7,11,15,19,23,27,31,35,39-Decamethyl-2,6,10,14,18,22,26,30,34,38-tetracontadecaenyl)-5,6-dimethoxy-3-methyl-P-benzoquinone

2,3-Dimethoxy-5-methyl-6-decaprenylbenzoquinone

2-[(2E,6E,10E,14E,18E,22E,26E,30E,34E)-3,7,11,15,19,23,27,31,35,39-Decamethyl-2,6,10,14,18,22,26,30,34,38-tetracontadecaenyl]-5,6-dimethoxy-3-methyl- 2,5-cyclohexadiene-1,4-dione

2-[(2E,6E,10E,14E,18E,22E,26E,30E,34E)-3,7,11,15,19,23,27,31,35,39-Decamethyltetraconta-2,6,10,14,18,22,26,30,34,38-decaen-1-yl]-5,6-dimethoxy-3-methyl-1,4-benzoquinone

4-Ethyl-5-fluoropyrimidine

Adelir

all-trans-Ubiquinone

Aqua Q 10l10

Aqua Q10

bio-Quinon

bio-Quinone Q10

Coenzyme Q10

Coenzyme Q-10

CO-Enzyme Q10

Coenzyme Q10, (Z,Z,Z,Z,Z,Z,e,e,e)-isomer

Coenzyme Q10, ion (1-), (all-e)-isomer

CoQ

CoQ 10

CoQ10

Ensorb

Kaneka Q10

Kudesan

Li-Q-sorb

Liquid-Q

Neuquinon

Neuquinone

PureSorb Q 40

Q 10AA

Q 199

Q10

Q-Gel

Q-Gel 100

Q-Ter

Ubidecarenone

Ubiquinone

Ubiquinone 10

Ubiquinone 50

Ubiquinone Q10

UBIQUINONE-10

Ubisemiquinone

Ubisemiquinone radical

Unbiquinone

Unispheres Q 10

Ubiquinone

Interventional clinical trials:

#	Name	Status	NCT ID	Phase	Drugs
1	A Phase Ia/Ib, Multiple-site Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KL1333 After a Single and Multiple Ascending Oral Doses in Healthy Subjects and Patients With Primary Mitochondrial Disease	Recruiting	NCT03888716	Phase 1	KL1333;Placebo Oral Tablet
2	Clinical Characteristics and Prognostic Factors of Mitochondrial nt3243 A>G Mutation in Taiwan	Unknown status	NCT02114554
3	Magnetic Resonance Imaging Study of Patients With Chronic Progressive External Ophthalmoplegia	Completed	NCT02161848
4	Effect Of The System In The Enriched Fat Metabolism Of The Child Reached Mitochondrial Cytopathy	Completed	NCT02385565
5	Nutritional Assessment in Patients Affected by Mitochondrial Cytopathy	Completed	NCT02375438
6	Can Metagenomic and Metadata be Combined Using Bioinformatics and Computational Biology Methods to Personalise Patient Treatment.	Completed	NCT03213067
7	North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC)	Recruiting	NCT01694940
8	Foundation Fighting Blindness Registry, My Retina Tracker	Recruiting	NCT02435940
9	Rare Disease Clinical Research Network Natural History of Pearson Syndrome North American Mitochondrial Disease Consortium (NAMDC)	Enrolling by invitation	NCT02327364

Search NIH Clinical Center for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4

Sources

Genetic Tests for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Genetic tests related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

#	Genetic test	Affiliating Genes
1	Autosomal Dominant Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 4 ²⁹	POLG2

Sources

Anatomical Context for Progressive External Ophthalmoplegia with Mitochondrial Dna...

MalaCards organs/tissues related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

⁴⁰

Skeletal Muscle, Liver, Eye, Retina, Brain, Heart, Thyroid

Sources

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Articles related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

(show top 50) (show all 517)

#	Title	Authors	PMID	Year
1	Biochemical analysis of human POLG2 variants associated with mitochondrial disease. ⁶ ⁵⁶	Young MJ...Copeland WC	21555342	2011
2	Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. ⁵⁶ ⁶	Longley MJ...Chinnery PF	16685652	2006
3	Mitochondrial DNA Maintenance Defects Overview ⁶	El-Hattab AW...Scaglia F	29517884	2018
4	Analysis of protein-coding genetic variation in 60,706 humans. ⁶	Lek M...Exome Aggregation Consortium	27535533	2016
5	Increased intra-mitochondrial lipofuscin aggregates with spherical dense body formation in mitochondrial myopathy. ⁶¹	Lu JQ...Tarnopolsky MA	32272361	2020
6	Severe Chronic Progressive External Ophthalmoplegia-Associated Ptosis Successfully Treated With Scleral Lenses. ⁶¹	Cherny C...Dagi Glass LR	32349064	2020
7	Cognitive Profile of Patients With Mitochondrial Chronic Progressive External Ophthalmoplegia. ⁶¹	Zhang G...Ye Z	32063883	2020
8	Chronic Progressive External Ophthalmoplegia due to a Rare de novo m.12334G>A MT-TL2 Mitochondrial DNA Variant1. ⁶¹	O'Donnell L...Murphy SM	32310184	2020
9	Neurodegenerative Diseases Associated with Mitochondrial DNA Mutations. ⁶¹	Zhunina OA...Orekhov AN	31755379	2020
10	Pediatric liver diseases and ocular changes: What hepatologists and ophthalmologists should know and share with each other. ⁶¹	Vitiello L...Vajro P	31843253	2020
11	Genotypes of chronic progressive external ophthalmoplegia in a large adult-onset cohort. ⁶¹	Heighton JN...Tarnopolsky MA	31521625	2019
12	Exophthalmos in Kearns-Sayre syndrome. ⁶¹	Tauber J...Park S	31158487	2019
13	A novel mitochondrial m.4414T>C MT-TM gene variant causing progressive external ophthalmoplegia and myopathy. ⁶¹	Hellebrekers DMEI...Taylor RW	31488384	2019
14	A PRIMPOL mutation and variants in multiple genes may contribute to phenotypes in a familial case with chronic progressive external ophthalmoplegia symptoms. ⁶¹	Kasamo K...Sano A	31348995	2019
15	Chronic Progressive External Ophthalmoplegia and Bilateral Vestibular Hypofunction: Balance, Gait, and Eye Movement Before and After Multimodal Chiropractic Care: A Case Study. ⁶¹	Russell BS...Drake ED	31367202	2019
16	Distinct segregation of the pathogenic m.5667G>A mitochondrial tRNAAsn mutation in extraocular and skeletal muscle in chronic progressive external ophthalmoplegia. ⁶¹	Schlapakow E...Kunz WS	30962064	2019
17	Optical coherence tomography findings in chronic progressive external ophthalmoplegia. ⁶¹	Wu Y...Wang ZX	31140991	2019
18	Muscle pain in mitochondrial diseases: a picture from the Italian network. ⁶¹	Filosto M...Mancuso M	30710167	2019
19	Late-onset presentation of POLG1-associated mitochondrial disease. ⁶¹	Meira B...Caetano A	30936349	2019
20	[Mitochondrial diseases]. ⁶¹	Radelfahr F...Klopstock T	30643957	2019
21	CPEO and Mitochondrial Myopathy in a Patient with DGUOK Compound Heterozygous Pathogenetic Variant and mtDNA Multiple Deletions. ⁶¹	Montano V...Mancuso M	30956829	2019
22	A rare case of mitochondriopathy with autosomal dominant progressive external ophthalmoplegia diagnosed through skeletal muscle biopsy. ⁶¹	Bastian AE...Oprisan LA	31263856	2019
23	Appendicular skeletal muscle mass: A more sensitive biomarker of disease severity than BMI in adults with mitochondrial diseases. ⁶¹	Hou Y...Wang Z	31344055	2019
24	Teaching Video NeuroImages: MT-TL1 mutation presenting as chronic progressive external ophthalmoplegia. ⁶¹	Parsons AM...Dhamija R	30665919	2019
25	Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort. ⁶¹	Heighton JN...Tarnopolsky MA	29246868	2019
26	Strabismus surgery for diplopia in chronic progressive external ophthalmoplegia. ⁶¹	Chatzistefanou KI...Koutsandrea C	29582258	2019
27	Ophthalmoplegia in Mitochondrial Disease. ⁶¹	Lee SJ...Lee YM	30450853	2018
28	Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder. ⁶¹	Kato TM...Kato T	29892051	2018
29	Intracranial hypotension mimicking chronic progressive external ophthalmoplegia. ⁶¹	Vahdani K...Garrott H	29300676	2018
30	Novel mutation in the RNASEH1 gene in a chronic progressive external ophthalmoplegia patient. ⁶¹	Sachdev A...McMullan TFW	30340744	2018
31	False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature. ⁶¹	Rajput R...Murray A	29333908	2018
32	[Diagnostic and Therapeutic Approaches for Mitochondrial Diseases]. ⁶¹	Radelfahr F...Klopstock T	30248691	2018
33	Phenotypic and Genotypic Heterogeneity of RRM2B Variants. ⁶¹	Finsterer J...Zarrouk-Mahjoub S	29241262	2018
34	Progressive fat replacement of muscle contributes to the disease mechanism of patients with single, large-scale deletions of mitochondrial DNA. ⁶¹	Hedermann G...Vissing J	29567350	2018
35	Disclosing the functional changes of two genetic alterations in a patient with Chronic Progressive External Ophthalmoplegia: Report of the novel mtDNA m.7486G>A variant. ⁶¹	Bacalhau M...Grazina M	29398297	2018
36	[Mitochondrial Dysfunctions and Role of Coenzyme Q10 in Patients with Glaucoma]. ⁶¹	Erb C...Konieczka K	29448286	2018
37	Mitochondrial Disorder: Kearns-Sayre Syndrome. ⁶¹	Tsang SH...Sharma T	30578503	2018
38	Outcome of epilepsy in patients with mitochondrial disorders: Phenotype genotype and magnetic resonance imaging correlations. ⁶¹	Bindu PS...Taly AB	29272804	2018
39	Anesthetic management of a parturient with Kearns-Sayre syndrome, dual-chamber and VVI implantable defibrillator pacemaker/defibrillator, and preeclampsia for cesarean delivery: A case report and review of the literature. ⁶¹	Al Ghamdi A	29416473	2018
40	Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. ⁶¹	Narumi K...Ito S	29190634	2018
41	[Chronic Progressive External Ophthalmoplegia Ptosis: Problems with Diagnostics and Treatment]. ⁶¹	Pfeiffer MJ	29373868	2018
42	Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA. ⁶¹	Nicholls TJ...Gustafsson CM	29290614	2018
43	Mitochondrial mutations in 12S rRNA and 16S rRNA presenting as chronic progressive external ophthalmoplegia (CPEO) plus: A case report. ⁶¹	Lv ZY...Hao YL	29310369	2017
44	Surgical Technique for Pulled in Two Syndrome: Three Cases With Chronic Progressive External Ophthalmoplegia. ⁶¹	Jones AM...Tan K	29156062	2017
45	Clinical, biochemical, molecular, and histological features of 65 Portuguese patients with mitochondrial disorders. ⁶¹	Cruz S...Vilarinho L	28128857	2017
46	Pure exercise intolerance and ophthalmoplegia associated with the m.12,294G > A mutation in the MT-TL2 gene: a case report. ⁶¹	Soldath P...Vissing J	29052516	2017
47	Reply to "Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia". ⁶¹	Gueguen A...Bostock H	28838816	2017
48	Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia. ⁶¹	Finsterer J...Zarrouk-Mahjoub S	28811105	2017
49	Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice. ⁶¹	Morovat A...Poulton J	28825656	2017
50	Mitochondrial dysfunction and cerebral metabolic abnormalities in patients with mitochondrial encephalomyopathy subtypes: Evidence from proton MR spectroscopy and muscle biopsy. ⁶¹	Niu FN...Xu Y	28695670	2017

Sources

Genes for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Genes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 (1 elite genes):

(show all 16)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	POLG2	DNA Polymerase Gamma 2, Accessory Subunit	Protein Coding	1326.32	Molecular basis known ⁵⁶ Pathogenic ⁶ Causative variation ⁷³ Genetic Tests ²⁹ DISEASES inferred ¹⁵ GeneCards inferred via : Disorders Variants (show sections)	16685652 27535533 21555342 (more) 29517884
2	SUCLG1	Succinate-CoA Ligase GDP/ADP-Forming Subunit Alpha	Protein Coding	6.48	DISEASES inferred ¹⁵
3	DGUOK	Deoxyguanosine Kinase	Protein Coding	6.48	DISEASES inferred ¹⁵
4	RRM2B	Ribonucleotide Reductase Regulatory TP53 Inducible Subunit M2B	Protein Coding	6.26	DISEASES inferred ¹⁵
5	INTS2	Integrator Complex Subunit 2	Protein Coding	6.12	DISEASES inferred ¹⁵
6	MPV17	Mitochondrial Inner Membrane Protein MPV17	Protein Coding	5.96	DISEASES inferred ¹⁵
7	TYMP	Thymidine Phosphorylase	Protein Coding	5.68	DISEASES inferred ¹⁵
8	SUCLA2	Succinate-CoA Ligase ADP-Forming Subunit Beta	Protein Coding	5.63	DISEASES inferred ¹⁵
9	TWNK	Twinkle MtDNA Helicase	Protein Coding	5.19	DISEASES inferred ¹⁵
10	SSBP1	Single Stranded DNA Binding Protein 1	Protein Coding	5.14	DISEASES inferred ¹⁵
11	POLG	DNA Polymerase Gamma, Catalytic Subunit	Protein Coding	4.99	DISEASES inferred ¹⁵
12	SLC25A4	Solute Carrier Family 25 Member 4	Protein Coding	4.86	DISEASES inferred ¹⁵
13	IMMT	Inner Membrane Mitochondrial Protein	Protein Coding	4.32	DISEASES inferred ¹⁵
14	MT-ND2	Mitochondrially Encoded NADH:Ubiquinone Oxidoreductase Core Subunit 2	Protein Coding	4.31	DISEASES inferred ¹⁵
15	SOX17	SRY-Box Transcription Factor 17	Protein Coding	4.22	DISEASES inferred ¹⁵
16	FASLG	Fas Ligand	Protein Coding	3.26	DISEASES inferred ¹⁵

Sources

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

ClinVar genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

⁶ (show all 26) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	GRCh37 Pos	GRCh38 Pos
1	POLG2	NM_007215.4(POLG2):c.1352G>A (p.Gly451Glu)	SNV	Pathogenic	5276	rs104894632	17:62474046-62474046	17:64477929-64477929
2	POLG2	NM_007215.4(POLG2):c.614C>G (p.Pro205Arg)	SNV	Pathogenic	40247	rs397514659	17:62489087-62489087	17:64492970-64492970
3	POLG2	NM_007215.4(POLG2):c.1423_1424del (p.Leu475fs)	deletion	Pathogenic	40249	rs1568079613	17:62473974-62473975	17:64477857-64477858
4	POLG2	NM_007215.4(POLG2):c.1105A>G (p.Arg369Gly)	SNV	Conflicting interpretations of pathogenicity	40248	rs201936720	17:62481850-62481850	17:64485733-64485733
5	MILR1 , POLG2	NM_007215.4(POLG2):c.1417G>A (p.Asp473Asn)	SNV	Conflicting interpretations of pathogenicity	215019	rs563130304	17:62473981-62473981	17:64477864-64477864
6	POLG2	NM_007215.4(POLG2):c.181G>A (p.Gly61Arg)	SNV	Conflicting interpretations of pathogenicity	215022	rs144148008	17:62492906-62492906	17:64496788-64496788
7	POLG2	NM_007215.4(POLG2):c.674G>A (p.Arg225Gln)	SNV	Conflicting interpretations of pathogenicity	324559	rs148101254	17:62489027-62489027	17:64492910-64492910
8	POLG2	NM_007215.4(POLG2):c.562+11C>T	SNV	Conflicting interpretations of pathogenicity	384209	rs782336056	17:62492514-62492514	17:64496396-64496396
9	POLG2	NM_007215.4(POLG2):c.970-4G>A	SNV	Uncertain significance	889721		17:62481989-62481989	17:64485872-64485872
10	POLG2	NM_007215.4(POLG2):c.-85C>T	SNV	Uncertain significance	324565	rs886053252	17:62493171-62493171	17:64497053-64497053
11	POLG2	NM_007215.4(POLG2):c.358G>A (p.Val120Met)	SNV	Uncertain significance	324561	rs782034872	17:62492729-62492729	17:64496611-64496611
12	POLG2	NM_007215.4(POLG2):c.-66C>T	SNV	Uncertain significance	324563	rs886053251	17:62493152-62493152	17:64497034-64497034
13	POLG2	NM_007215.4(POLG2):c.673C>T (p.Arg225Ter)	SNV	Uncertain significance	488881	rs371515325	17:62489028-62489028	17:64492911-64492911
14	POLG2	NM_007215.4(POLG2):c.1343_1347del (p.Thr447_Leu448insTer)	deletion	Uncertain significance	632287	rs1568079693	17:62474051-62474055	17:64477934-64477938
15	POLG2	NM_007215.4(POLG2):c.1315T>C (p.Phe439Leu)	SNV	Uncertain significance	889720		17:62474083-62474083	17:64477966-64477966
16	POLG2	NM_007215.4(POLG2):c.381G>A (p.Pro127=)	SNV	Uncertain significance	891271		17:62492706-62492706	17:64496588-64496588
17	POLG2	NM_007215.4(POLG2):c.366G>T (p.Arg122Ser)	SNV	Uncertain significance	891272		17:62492721-62492721	17:64496603-64496603
18	POLG2	NM_007215.4(POLG2):c.496C>G (p.Gln166Glu)	SNV	Likely benign	324560	rs370683331	17:62492591-62492591	17:64496473-64496473
19	POLG2	NM_007215.4(POLG2):c.457C>G (p.Leu153Val)	SNV	Benign/Likely benign	215017	rs149446102	17:62492630-62492630	17:64496512-64496512
20	POLG2	NM_007215.4(POLG2):c.1247G>C (p.Gly416Ala)	SNV	Benign/Likely benign	138783	rs17850455	17:62476451-62476451	17:64480334-64480334
21	POLG2	NM_007215.4(POLG2):c.1269C>T (p.Ser423=)	SNV	Benign	138784	rs61733782	17:62476429-62476429	17:64480312-64480312
22	POLG2	NM_007215.4(POLG2):c.397C>T (p.His133Tyr)	SNV	Benign	215023	rs112984118	17:62492690-62492690	17:64496572-64496572
23	POLG2	NM_007215.4(POLG2):c.-81T>C	SNV	Benign	324564	rs9897606	17:62493167-62493167	17:64497049-64497049
24	POLG2	NM_007215.4(POLG2):c.-70T>C	SNV	Benign	892465		17:62493156-62493156	17:64497038-64497038
25	POLG2	NM_007215.4(POLG2):c.505G>A (p.Ala169Thr)	SNV	Benign	138782	rs1427463	17:62492582-62492582	17:64496464-64496464
26	POLG2	NM_007215.4(POLG2):c.-61G>A	SNV	Benign	324562	rs552693721	17:62493147-62493147	17:64497029-64497029

UniProtKB/Swiss-Prot genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

⁷³

#	Symbol	AA change	Variation ID	SNP ID
1	POLG2	p.Gly451Glu	VAR_029364	rs104894632

Sources

Expression for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Search GEO for disease gene expression data for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4.

Sources

Pathways for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Pathways related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Mitochondrial Gene Expression ¹ Show member pathways Activation of PPARGC1A (PGC-1alpha) by phosphorylation ⁶⁵ Mitochondrial biogenesis ⁶⁵ Mitochondrial transcription initiation ⁶⁵ Mitochondrial transcription termination ⁶⁵ Transcription from mitochondrial promoters ⁶⁵ Transcriptional activation of mitochondrial biogenesis ⁶⁵	11.27	TWNK SSBP1 POLG2
2	Propanoate metabolism ³⁶	10.79	SUCLG1 SUCLA2
3	Valproic Acid Pathway, Pharmacodynamics ⁶⁰ Show member pathways aspartate biosynthesis ¹	10.48	SUCLG1 SUCLA2
4	Nucleotide Metabolism ¹	9.9	RRM2B POLG

Sources

GO Terms for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Cellular components related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	mitochondrial matrix	GO:0005759	9.63	TWNK SUCLG1 SUCLA2 SSBP1 POLG2 DGUOK
2	mitochondrial inner membrane	GO:0005743	9.62	SLC25A4 MT-ND2 MPV17 IMMT
3	mitochondrion	GO:0005739	9.4	TWNK SUCLG1 SUCLA2 SSBP1 SLC25A4 RRM2B
4	gamma DNA polymerase complex	GO:0005760	9.26	POLG2 POLG
5	mitochondrial nucleoid	GO:0042645	9.26	TWNK SSBP1 POLG2 POLG

Biological processes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 according to GeneCards Suite gene sharing:

(show all 11)

#	Name	GO ID	Score	Top Affiliating Genes
1	mitochondrion organization	GO:0007005	9.58	TWNK SSBP1 POLG2
2	DNA biosynthetic process	GO:0071897	9.49	POLG2 POLG
3	tricarboxylic acid cycle	GO:0006099	9.48	SUCLG1 SUCLA2
4	DNA-dependent DNA replication	GO:0006261	9.46	POLG2 POLG
5	DNA unwinding involved in DNA replication	GO:0006268	9.43	TWNK SSBP1
6	mitochondrion morphogenesis	GO:0070584	9.43	SSBP1 POLG2 IMMT
7	succinate metabolic process	GO:0006105	9.37	SUCLG1 SUCLA2
8	DNA replication	GO:0006260	9.35	TWNK SSBP1 RRM2B POLG2 POLG
9	mitochondrial genome maintenance	GO:0000002	9.33	TYMP SLC25A4 MPV17
10	succinyl-CoA metabolic process	GO:0006104	9.32	SUCLG1 SUCLA2
11	mitochondrial DNA replication	GO:0006264	9.02	TWNK SSBP1 RRM2B POLG2 POLG

Molecular functions related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 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	succinate-CoA ligase (GDP-forming) activity	GO:0004776	8.96	SUCLG1 SUCLA2
3	succinate-CoA ligase (ADP-forming) activity	GO:0004775	8.62	SUCLG1 SUCLA2

Sources

Sources for Progressive External Ophthalmoplegia with Mitochondrial Dna...

¹ BioSystems

² BitterDB

³ CDC

⁴ Cell Signaling Technology

⁵ ClinicalTrials

⁶ ClinVar

⁷ CNVD

⁸ Cochrane Library

⁹ Cosmic

¹⁰ dbSNP

¹¹ DGIdb

¹² Disease Ontology

¹³ diseasecard

¹⁴ DiseaseEnhancer

¹⁵ DISEASES

¹⁶ DrugBank

¹⁷ EFO

¹⁸ ExPASy

¹⁹ FMA

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ Genetics Home Reference

²⁶ GenomeRNAi

²⁷ GEO DataSets

²⁸ GO

²⁹ GTR

³⁰ HMDB

³¹ HPO

³² ICD10

³³ ICD10 via Orphanet

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ KEGG

³⁷ LifeMap

³⁸ LncRNADisease

³⁹ LOVD

⁴⁰ MalaCards

⁴¹ MedGen

⁴² MedlinePlus

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NIH Rare Diseases

⁵³ NINDS

⁵⁴ Novoseek

⁵⁵ Novus Biologicals

⁵⁶ OMIM

⁵⁷ OMIM via Orphanet

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubMed

⁶² PubMed Health

⁶³ QIAGEN

⁶⁴ R&D Systems

⁶⁵ Reactome

⁶⁶ Sino Biological

⁶⁷ SNOMED-CT

⁶⁸ SNOMED-CT via HPO

⁶⁹ TGDB

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ Wikipedia

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 (PEOA4)

Aliases & Classifications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

MalaCards integrated aliases for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Characteristics:

OMIM:

HPO:

Classifications:

External Ids:

Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Related Diseases for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Diseases in the Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1 family:

Diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 via text searches within MalaCards or GeneCards Suite gene sharing:

Graphical network of the top 20 diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Symptoms & Phenotypes for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Human phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Symptoms via clinical synopsis from OMIM:

Clinical features from OMIM:

UMLS symptoms related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

MGI Mouse Phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Drugs & Therapeutics for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Drugs for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

Interventional clinical trials:

Genetic Tests for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Genetic tests related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Anatomical Context for Progressive External Ophthalmoplegia with Mitochondrial Dna...

MalaCards organs/tissues related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Articles related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Genes for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Genes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 (1 elite genes):

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

ClinVar genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

UniProtKB/Swiss-Prot genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4:

Expression for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Pathways for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Pathways related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 according to GeneCards Suite gene sharing:

GO Terms for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Cellular components related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 according to GeneCards Suite gene sharing:

Biological processes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 according to GeneCards Suite gene sharing:

Molecular functions related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 4 according to GeneCards Suite gene sharing:

Sources for Progressive External Ophthalmoplegia with Mitochondrial Dna...