PEOA4
MCID: PRG040
MIFTS: 42

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

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
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:



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 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1, 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). The drug Ubiquinone has been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, eye and liver, and related phenotypes are seizures and failure to thrive

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)

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 123)
# Related Disease Score Top Affiliating Genes
1 chronic progressive external ophthalmoplegia 13.1
2 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1 12.4
3 kearns-sayre syndrome 12.4
4 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 2 12.4
5 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3 12.4
6 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 1 12.2
7 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2 12.2
8 ocular muscular dystrophy 11.9
9 mitochondrial dna-related progressive external ophthalmoplegia 11.9
10 strabismus 11.7
11 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 11.7
12 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 5 11.4
13 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 6 11.4
14 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 3 11.4
15 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 4 11.4
16 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 5 11.4
17 ptosis 10.8
18 myopathy 10.8
19 mitochondrial myopathy 10.7
20 mitochondrial disorders 10.6
21 mitochondrial metabolism disease 10.5
22 dysphagia 10.5
23 mitochondrial encephalomyopathy 10.4
24 mechanical strabismus 10.4
25 branchiootic syndrome 1 10.4
26 neuropathy 10.4
27 ataxia and polyneuropathy, adult-onset 10.3
28 optic nerve disease 10.3
29 lactic acidosis 10.3
30 myasthenia gravis 10.3
31 retinitis pigmentosa 10.3
32 aceruloplasminemia 10.3
33 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.3
34 neuroretinitis 10.3
35 alternating exotropia 10.3
36 exotropia 10.3
37 retinitis 10.3
38 encephalopathy 10.3
39 hereditary optic neuropathy 10.3
40 3-methylglutaconic aciduria, type iii 10.2
41 lagophthalmos 10.2
42 peripheral nervous system disease 10.2
43 keratitis, hereditary 10.1
44 optic atrophy 1 10.1
45 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 10.1
46 atrioventricular block 10.1
47 sensorineural hearing loss 10.1
48 movement disease 10.1
49 exophthalmos 10.1
50 exposure keratitis 10.1

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

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

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
1 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

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

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, Eye, Liver, Heart, Retina, Brain, Thyroid

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 515)
# Title Authors PMID Year
1
Biochemical analysis of human POLG2 variants associated with mitochondrial disease. 56 6
21555342 2011
2
Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. 56 6
16685652 2006
3
Mitochondrial DNA Maintenance Defects Overview 6
29517884 2018
4
Analysis of protein-coding genetic variation in 60,706 humans. 6
27535533 2016
5
Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia. 6
21951382 2011
6
RRM2B mutations are frequent in familial PEO with multiple mtDNA deletions. 6
21646632 2011
7
Pediatric liver diseases and ocular changes: What hepatologists and ophthalmologists should know and share with each other. 61
31843253 2020
8
Neurodegenerative diseases associated with mitochondrial DNA mutations. 61
31755379 2019
9
Genotypes of chronic progressive external ophthalmoplegia in a large adult-onset cohort. 61
31521625 2019
10
Exophthalmos in Kearns-Sayre syndrome. 61
31158487 2019
11
A novel mitochondrial m.4414T>C MT-TM gene variant causing progressive external ophthalmoplegia and myopathy. 61
31488384 2019
12
A PRIMPOL mutation and variants in multiple genes may contribute to phenotypes in a familial case with chronic progressive external ophthalmoplegia symptoms. 61
31348995 2019
13
Chronic Progressive External Ophthalmoplegia and Bilateral Vestibular Hypofunction: Balance, Gait, and Eye Movement Before and After Multimodal Chiropractic Care: A Case Study. 61
31367202 2019
14
Distinct segregation of the pathogenic m.5667G>A mitochondrial tRNAAsn mutation in extraocular and skeletal muscle in chronic progressive external ophthalmoplegia. 61
30962064 2019
15
Optical coherence tomography findings in chronic progressive external ophthalmoplegia. 61
31140991 2019
16
Muscle pain in mitochondrial diseases: a picture from the Italian network. 61
30710167 2019
17
Late-onset presentation of POLG1-associated mitochondrial disease. 61
30936349 2019
18
[Mitochondrial diseases]. 61
30643957 2019
19
CPEO and Mitochondrial Myopathy in a Patient with DGUOK Compound Heterozygous Pathogenetic Variant and mtDNA Multiple Deletions. 61
30956829 2019
20
A rare case of mitochondriopathy with autosomal dominant progressive external ophthalmoplegia diagnosed through skeletal muscle biopsy. 61
31263856 2019
21
Appendicular skeletal muscle mass: A more sensitive biomarker of disease severity than BMI in adults with mitochondrial diseases. 61
31344055 2019
22
Strabismus surgery for diplopia in chronic progressive external ophthalmoplegia. 61
29582258 2019
23
Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort. 61
29246868 2019
24
Teaching Video NeuroImages: MT-TL1 mutation presenting as chronic progressive external ophthalmoplegia. 61
30665919 2019
25
Ophthalmoplegia in Mitochondrial Disease. 61
30450853 2018
26
Ant1 mutant mice bridge the mitochondrial and serotonergic dysfunctions in bipolar disorder. 61
29892051 2018
27
Novel mutation in the RNASEH1 gene in a chronic progressive external ophthalmoplegia patient. 61
30340744 2018
28
False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature. 61
29333908 2018
29
Intracranial hypotension mimicking chronic progressive external ophthalmoplegia. 61
29300676 2018
30
[Diagnostic and Therapeutic Approaches for Mitochondrial Diseases]. 61
30248691 2018
31
Phenotypic and Genotypic Heterogeneity of RRM2B Variants. 61
29241262 2018
32
Progressive fat replacement of muscle contributes to the disease mechanism of patients with single, large-scale deletions of mitochondrial DNA. 61
29567350 2018
33
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
29398297 2018
34
[Mitochondrial Dysfunctions and Role of Coenzyme Q10 in Patients with Glaucoma]. 61
29448286 2018
35
Mitochondrial Disorder: Kearns-Sayre Syndrome. 61
30578503 2018
36
Outcome of epilepsy in patients with mitochondrial disorders: Phenotype genotype and magnetic resonance imaging correlations. 61
29272804 2018
37
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
29416473 2018
38
Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. 61
29190634 2018
39
[Chronic Progressive External Ophthalmoplegia Ptosis: Problems with Diagnostics and Treatment]. 61
29373868 2018
40
Topoisomerase 3α Is Required for Decatenation and Segregation of Human mtDNA. 61
29290614 2018
41
Mitochondrial mutations in 12S rRNA and 16S rRNA presenting as chronic progressive external ophthalmoplegia (CPEO) plus: A case report. 61
29310369 2017
42
Surgical Technique for Pulled in Two Syndrome: Three Cases With Chronic Progressive External Ophthalmoplegia. 61
29156062 2017
43
Clinical, biochemical, molecular, and histological features of 65 Portuguese patients with mitochondrial disorders. 61
28128857 2017
44
Pure exercise intolerance and ophthalmoplegia associated with the m.12,294G > A mutation in the MT-TL2 gene: a case report. 61
29052516 2017
45
Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia. 61
28811105 2017
46
Reply to "Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia". 61
28838816 2017
47
Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice. 61
28825656 2017
48
Mitochondrial dysfunction and cerebral metabolic abnormalities in patients with mitochondrial encephalomyopathy subtypes: Evidence from proton MR spectroscopy and muscle biopsy. 61
28695670 2017
49
A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma. 61
28430993 2017
50
Efficacy of frontalis suspension with silicone rods in ptosis patients with poor Bell's phenomenon. 61
29034153 2017

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# 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 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.673C>T (p.Arg225Ter)SNV Uncertain significance 488881 rs371515325 17:62489028-62489028 17:64492911-64492911
7 POLG2 NM_007215.4(POLG2):c.1343_1347del (p.Thr447_Leu448insTer)deletion Uncertain significance 632287 rs1568079693 17:62474051-62474055 17:64477934-64477938

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

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.

Pathways for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

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