MCID: PRG130
MIFTS: 36

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1

Categories: Genetic diseases

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

MalaCards integrated aliases for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:

Name: Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1 57
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant, 1 75 73
Autosomal Dominant Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 1 29 6
Chronic Progressive External Ophthalmoplegia 75 73
Peoa1 57 75
Ophthalmoplegia, External, Progressive, with Mitochondrial Dna Deletions, Autosomal Dominant, Type 1 40
Progressive External Ophthalmoplegia, Autosomal Dominant 1 57
Progressive External Ophthalmoplegia, Autosomal Dominant 13
Progressive External Ophthalmoplegia Autosomal Dominant 75
Ocular Myopathy of Von Graefe-Fuchs 75
Mitochondrial Ocular Myopathy 75
Kearns-Sayre Syndrome 73
Graefe Disease 75
Cpeo 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
adult onset
progressive disorder
highly variable phenotype
incidence of 1/100,000 in italy and finland
patients often have a more severe and complicated phenotype in addition to peo
hypogonadism reported in a large swedish kindred
see also autosomal recessive peob ({258450)}
genetic heterogeneity (see peoa2 )
polg mutations account for approximately 45% of all peo cases


HPO:

32
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1:
Onset and clinical course adult onset phenotypic variability progressive
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

UniProtKB/Swiss-Prot : 75 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1: 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 1, also known as progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 1, is related to chronic progressive external ophthalmoplegia and kearns-sayre syndrome, and has symptoms including cerebellar ataxia, seizures and muscle weakness. An important gene associated with Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1 is POLG (DNA Polymerase Gamma, Catalytic Subunit). Affiliated tissues include skeletal muscle, eye and retina, and related phenotypes are ptosis and depressivity

OMIM : 57 Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Both autosomal dominant and autosomal recessive inheritance can occur; autosomal recessive inheritance is usually more severe (Filosto et al., 2003; Luoma et al., 2004). PEO caused by mutation in the POLG gene is associated with more complicated phenotypes than those forms caused by mutation in the ANT1 or C10ORF2 genes (Lamantea et al., 2002). (157640)

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

Graphical network of the top 20 diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:



Diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
external ophthalmoplegia, progressive (peo)
cataracts (later onset)

Abdomen Gastrointestinal:
dysphagia
gastroparesis
gastrointestinal pseudoobstruction

Skeletal Feet:
pes cavus

Muscle Soft Tissue:
exercise intolerance
limb muscle weakness
muscle atrophy
facial muscle weakness
muscle weakness, progressive
more
Head And Neck Ears:
sensorineural hearing loss

Genitourinary Internal Genitalia Female:
premature ovarian failure (in a subset of patients)

Neurologic Central Nervous System:
ataxia
dysarthria
rigidity
bradykinesia
resting tremor
more
Neurologic Peripheral Nervous System:
gait ataxia
sensory axonal neuropathy
hyporeflexia
distal sensory loss of proprioception and vibration sense

Laboratory Abnormalities:
increased serum lactate
rhabdomyolysis in response to alcohol

Neurologic Behavioral Psychiatric Manifestations:
depression

Genitourinary External Genitalia Male:
testicular atrophy (in a subset of patients)

Endocrine Features:
primary amenorrhea (in a subset of patients)
secondary amenorrhea (in a subset of patients)
premature menopause (in a subset of patients)
hypergonadotropic hypogonadism (in a subset of patients)
decreased secondary sexual characteristics (in a subset of patients)


Clinical features from OMIM:

157640

Human phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:

32 (show all 36)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 depressivity 32 HP:0000716
3 dysarthria 32 HP:0001260
4 dysphagia 32 HP:0002015
5 facial palsy 32 HP:0010628
6 cataract 32 HP:0000518
7 sensorineural hearing impairment 32 HP:0000407
8 skeletal muscle atrophy 32 HP:0003202
9 premature ovarian insufficiency 32 HP:0008209
10 primary amenorrhea 32 HP:0000786
11 secondary amenorrhea 32 HP:0000869
12 gait ataxia 32 HP:0002066
13 pes cavus 32 HP:0001761
14 sensory axonal neuropathy 32 HP:0003390
15 increased serum lactate 32 HP:0002151
16 gastroparesis 32 HP:0002578
17 ragged-red muscle fibers 32 HP:0003200
18 progressive external ophthalmoplegia 32 HP:0000590
19 testicular atrophy 32 HP:0000029
20 rigidity 32 HP:0002063
21 hypergonadotropic hypogonadism 32 HP:0000815
22 hyporeflexia 32 HP:0001265
23 bradykinesia 32 HP:0002067
24 exercise intolerance 32 HP:0003546
25 limb muscle weakness 32 HP:0003690
26 parkinsonism with favorable response to dopaminergic medication 32 HP:0002548
27 increased variability in muscle fiber diameter 32 HP:0003557
28 progressive muscle weakness 32 HP:0003323
29 resting tremor 32 HP:0002322
30 impaired distal proprioception 32 HP:0006858
31 impaired distal vibration sensation 32 HP:0006886
32 muscle fiber necrosis 32 HP:0003713
33 emg 32 HP:0003458
34 subsarcolemmal accumulations of abnormally shaped mitochondria 32 HP:0003548
35 cytochrome c oxidase-negative muscle fibers 32 HP:0003688
36 multiple mitochondrial dna deletions 32 HP:0003689

UMLS symptoms related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:


cerebellar ataxia, seizures, muscle weakness, ophthalmoplegia, ataxia, muscle rigidity, bradykinesia, resting tremor, facial paresis, gait ataxia

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

Search Clinical Trials , NIH Clinical Center for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1

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

Genetic tests related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:

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

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

MalaCards organs/tissues related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:

41
Skeletal Muscle, Eye, Retina, Skin, Brain, Heart

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Articles related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:

(show top 50) (show all 164)
# Title Authors Year
1
Intracranial hypotension mimicking chronic progressive external ophthalmoplegia. ( 29300676 )
2018
2
False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature. ( 29333908 )
2018
3
Strabismus surgery for diplopia in chronic progressive external ophthalmoplegia. ( 29582258 )
2018
4
Mitochondrial mutations in 12S rRNA and 16S rRNA presenting as chronic progressive external ophthalmoplegia (CPEO) plus: A case report. ( 29310369 )
2017
5
Sporadic chronic progressive external ophthalmoplegia with single large mitochondrial DNA deletion and neurogenic findings. ( 28175988 )
2017
6
Unilateral Ptosis and Homolateral Hemifacial Weakness in Chronic Progressive External Ophthalmoplegia. ( 28512510 )
2017
7
Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia. ( 28811105 )
2017
8
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. ( 29398297 )
2017
9
Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. ( 29190634 )
2017
10
Surgical Technique for Pulled in Two Syndrome: Three Cases With Chronic Progressive External Ophthalmoplegia. ( 29156062 )
2017
11
Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort. ( 29246868 )
2017
12
Nerve excitability changes related to muscle weakness in chronic progressive external ophthalmoplegia. ( 28535487 )
2017
13
A novel mitochondrial tRNA(Ala) gene variant causes chronic progressive external ophthalmoplegia in a patient with Huntington disease. ( 27014581 )
2016
14
Histopathological and genetic analysis of extraocular muscle in chronic progressive external ophthalmoplegia. ( 27470685 )
2016
15
Novel mutation in C10orf2 associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging. ( 26689116 )
2016
16
Multiple sclerosis and chronic progressive external ophthalmoplegia associated with a large scale mitochondrial DNA single deletion. ( 27113600 )
2016
17
Late-Onset Development of Eyelid Ptosis in Chronic Progressive External Ophthalmoplegia: A 30-Year Follow-up. ( 27928383 )
2016
18
Chronic Progressive External Ophthalmoplegia in the Absence of Ptosis. ( 27111092 )
2016
19
Vocal cord palsy in a case of chronic progressive external ophthalmoplegia. ( 26713034 )
2015
20
Pharyngeal transit in patients with chronic progressive external ophthalmoplegia. ( 25142449 )
2014
21
Cardiac involvement in chronic progressive external ophthalmoplegia. ( 25139213 )
2014
22
Novel mitochondrial tRNA(Ile) m.4282A>G gene mutation leads to chronic progressive external ophthalmoplegia plus phenotype. ( 25034047 )
2014
23
Chronic progressive external ophthalmoplegia with inflammatory myopathy. ( 25674260 )
2014
24
Selected Case From the Arkadi M. Rywlin International Pathology Slide Series: Mitochondrial Myopathy Presenting With Chronic Progressive External Ophthalmoplegia (CPEO): A Case Report. ( 25299315 )
2014
25
Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. ( 24727571 )
2014
26
Autosomal dominant mutations in POLG and C10orf2: association with late onset chronic progressive external ophthalmoplegia and Parkinsonism in two patients. ( 23719791 )
2013
27
Extraocular muscle atrophy and central nervous system involvement in chronic progressive external ophthalmoplegia. ( 24086434 )
2013
28
Chronic progressive external ophthalmoplegia coexistent with motor neuron disease in a patient with a novel large-scale mitochondrial DNA deletion. ( 23266267 )
2013
29
No association between mitochondrial tRNA(Val) T1658C mutation and chronic progressive external ophthalmoplegia (CPEO). ( 23815321 )
2013
30
Paralytic exophthalmos in chronic progressive external ophthalmoplegia. ( 22504268 )
2012
31
Sleep disturbances in chronic progressive external ophthalmoplegia. ( 21819490 )
2012
32
Diagnostic investigations of patients with chronic progressive external ophthalmoplegia. ( 23024221 )
2012
33
The mutations m.5628T>C and m.8348A>G in single muscle fibers of a patient with chronic progressive external ophthalmoplegia. ( 22743145 )
2012
34
Impairment of mitochondrial tRNAIle processing by a novel mutation associated with chronic progressive external ophthalmoplegia. ( 21292040 )
2011
35
Chronic progressive external ophthalmoplegia with T9957C mitochondrial DNA mutation in a Taiwanese patient. ( 21249588 )
2011
36
Multisystem disorder in late-onset chronic progressive external ophthalmoplegia. ( 21156440 )
2011
37
Esophageal contractions in patients with chronic progressive external ophthalmoplegia. ( 21399928 )
2011
38
Nature and frequency of respiratory involvement in chronic progressive external ophthalmoplegia. ( 21533826 )
2011
39
Disease impact in chronic progressive external ophthalmoplegia: more than meets the eye. ( 21236670 )
2011
40
A novel mitochondrial tRNA(Ile) point mutation associated with chronic progressive external ophthalmoplegia and hyperCKemia. ( 20884012 )
2011
41
Multiplex ligation-dependent probe amplification (MLPA) assay for the detection of mitochondrial DNA deletion in chronic progressive external ophthalmoplegia (CPEO). ( 22166510 )
2011
42
Morphological findings of extraocular myopathy with chronic progressive external ophthalmoplegia. ( 20192704 )
2010
43
Chronic progressive external ophthalmoplegia with recurrent quadriparesis : an unusual presentation. ( 21045517 )
2010
44
A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO). ( 20149659 )
2010
45
The management of strabismus in patients with chronic progressive external ophthalmoplegia. ( 20521878 )
2010
46
Eye movement recordings to investigate a supranuclear component in chronic progressive external ophthalmoplegia: a cross-sectional study. ( 20576783 )
2010
47
A novel mitochondrial tRNAGlu (MTTE) gene mutation causing chronic progressive external ophthalmoplegia at low levels of heteroplasmy in muscle. ( 20810132 )
2010
48
Molecular analysis in a family presenting with a mild form of late- onset autosomal dominant chronic progressive external ophthalmoplegia. ( 19428252 )
2009
49
Cystoid macular edema in a patient with chronic progressive external ophthalmoplegia with mitochondrial myopathy. ( 19172512 )
2009
50
Frontalis suspension sling using palmaris longus tendon in chronic progressive external ophthalmoplegia. ( 19300161 )
2009

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

UniProtKB/Swiss-Prot genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:

75
# Symbol AA change Variation ID SNP ID
1 POLG p.Tyr955Cys VAR_012156 rs113994099
2 POLG p.Gly923Asp VAR_023678
3 POLG p.Arg943His VAR_023680
4 POLG p.Arg953Cys VAR_023681 rs11546842
5 POLG p.Ala957Ser VAR_023682 rs121918051
6 POLG p.Ser1176Leu VAR_023690 rs776031396
7 POLG p.Ser511Asn VAR_058878 rs121918055
8 POLG p.Asp1186His VAR_065119

ClinVar genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1:

6
(show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 POLG NM_002693.2(POLG): c.2864A> G (p.Tyr955Cys) single nucleotide variant Pathogenic rs113994099 GRCh37 Chromosome 15, 89864114: 89864114
2 POLG NM_002693.2(POLG): c.2864A> G (p.Tyr955Cys) single nucleotide variant Pathogenic rs113994099 GRCh38 Chromosome 15, 89320883: 89320883
3 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic rs113994095 GRCh37 Chromosome 15, 89870432: 89870432
4 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic rs113994095 GRCh38 Chromosome 15, 89327201: 89327201
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.2869G> T (p.Ala957Ser) single nucleotide variant Pathogenic rs121918051 GRCh37 Chromosome 15, 89864109: 89864109
8 POLG NM_002693.2(POLG): c.2869G> T (p.Ala957Ser) single nucleotide variant Pathogenic rs121918051 GRCh38 Chromosome 15, 89320878: 89320878
9 POLG NM_002693.2(POLG): c.1532G> A (p.Ser511Asn) single nucleotide variant Pathogenic rs121918055 GRCh37 Chromosome 15, 89870196: 89870196
10 POLG NM_002693.2(POLG): c.1532G> A (p.Ser511Asn) single nucleotide variant Pathogenic rs121918055 GRCh38 Chromosome 15, 89326965: 89326965
11 POLG NM_002693.2(POLG): c.1174C> G (p.Leu392Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145289229 GRCh37 Chromosome 15, 89871763: 89871763
12 POLG NM_002693.2(POLG): c.1174C> G (p.Leu392Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145289229 GRCh38 Chromosome 15, 89328532: 89328532
13 POLG NM_002693.2(POLG): c.2207A> G (p.Asn736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs138457939 GRCh38 Chromosome 15, 89323462: 89323462
14 POLG NM_002693.2(POLG): c.2207A> G (p.Asn736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs138457939 GRCh37 Chromosome 15, 89866693: 89866693
15 POLG NM_002693.2(POLG): c.3612_3613insAACT (p.Gly1205Asnfs) insertion Pathogenic rs886043241 GRCh37 Chromosome 15, 89860637: 89860638
16 POLG NM_002693.2(POLG): c.3612_3613insAACT (p.Gly1205Asnfs) insertion Pathogenic rs886043241 GRCh38 Chromosome 15, 89317406: 89317407

Copy number variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 1 from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 244121 8 93300000 117700000 Copy number RRM2B Autosomal-dominant progressive external ophthalmoplegia

Expression for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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Pathways for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

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