PEOA2
MCID: PRG038
MIFTS: 41

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2 (PEOA2)

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic 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 2:

Name: Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2 57
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant, 2 75 73
Autosomal Dominant Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 2 29 6
Chronic Progressive External Ophthalmoplegia 75 73
Peoa2 57 75
Ophthalmoplegia, External, Progressive, with Mitochondrial Dna Deletions, Autosomal Dominant, Type 2 40
Progressive External Ophthalmoplegia, Autosomal Dominant 2 57
Progressive External Ophthalmoplegia Autosomal Dominant 2 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:
progressive disorder
genetic heterogeneity (see )
adult onset (before 50 years)
slc25a4 mutations account for approximately 4% of all peo cases


HPO:

32
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 2:
Onset and clinical course adult onset progressive
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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. 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 mutations in the POLG gene are associated with more complicated phenotypes than those forms caused by mutations in the ANT1 or C10ORF2 genes (Lamantea et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640). (609283)

MalaCards based summary : Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2, also known as progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 2, is related to chronic progressive external ophthalmoplegia and kearns-sayre syndrome, and has symptoms including seizures, muscle weakness and ophthalmoplegia. An important gene associated with Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2 is SLC25A4 (Solute Carrier Family 25 Member 4). Affiliated tissues include eye, skeletal muscle and bone, and related phenotypes are ptosis and facial palsy

UniProtKB/Swiss-Prot : 75 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2: 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.

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

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

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 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 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 chronic progressive external ophthalmoplegia 12.9
2 kearns-sayre syndrome 12.2
3 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1 12.0
4 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3 12.0
5 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 4 12.0
6 ocular muscular dystrophy 11.7
7 maternally-inherited progressive external ophthalmoplegia 11.7
8 strabismus 11.6
9 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 1 11.5
10 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2 11.4
11 ptosis 10.4
12 myopathy 10.4
13 mitochondrial myopathy 10.3
14 optic nerve disease 10.2
15 neuropathy 10.2
16 multiple sclerosis 10.1
17 polyglucosan body myopathy 1 with or without immunodeficiency 10.1
18 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
19 exotropia 10.1
20 atrial standstill 1 10.0
21 huntington disease 10.0
22 hypercholesterolemia, familial 10.0
23 macular dystrophy, dominant cystoid 10.0
24 retinitis pigmentosa 10.0
25 aging 10.0
26 focal segmental glomerulosclerosis 1 10.0
27 leber congenital amaurosis 4 10.0
28 focal segmental glomerulosclerosis 10.0
29 keratopathy 10.0
30 motor neuron disease 10.0
31 atrioventricular block 10.0
32 third-degree atrioventricular block 10.0
33 sensorineural hearing loss 10.0
34 retinitis 10.0
35 macular retinal edema 10.0
36 intracranial hypotension 10.0
37 mitochondrial metabolism disease 10.0
38 exophthalmos 10.0
39 mitochondrial disorders 10.0
40 encephalopathy 10.0
41 mitochondrial complex iv deficiency 9.9
42 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.9
43 peripheral nervous system disease 9.9
44 esotropia 9.9
45 dysphagia 9.9

Graphical network of the top 20 diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:



Diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2

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)

Head And Neck Ears:
sensorineural hearing loss has been reported

Muscle Soft Tissue:
facial muscle weakness
emg shows myopathic changes
muscle biopsy shows ragged red fibers
muscle biopsy shows multiple mitochondrial dna (mtdna) deletions
muscle biopsy shows decreased activity of cytochrome c oxidase
more
Laboratory Abnormalities:
serum lactate is usually normal


Clinical features from OMIM:

609283

Human phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 facial palsy 32 HP:0010628
3 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
4 generalized muscle weakness 32 HP:0003324
5 ragged-red muscle fibers 32 HP:0003200
6 progressive external ophthalmoplegia 32 HP:0000590
7 exercise intolerance 32 HP:0003546
8 cytochrome c oxidase-negative muscle fibers 32 HP:0003688
9 emg 32 HP:0003458
10 subsarcolemmal accumulations of abnormally shaped mitochondria 32 HP:0003548
11 multiple mitochondrial dna deletions 32 HP:0003689

UMLS symptoms related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:


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

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 2

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

Genetic tests related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:

# Genetic test Affiliating Genes
1 Autosomal Dominant Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 2 29 SLC25A4

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

MalaCards organs/tissues related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:

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

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Articles related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:

(show top 50) (show all 168)
# 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
Novel mutation in the RNASEH1 gene in a chronic progressive external ophthalmoplegia patient. ( 30340744 )
2018
5
Mitochondrial mutations in 12S rRNA and 16S rRNA presenting as chronic progressive external ophthalmoplegia (CPEO) plus: A case report. ( 29310369 )
2017
6
Sporadic chronic progressive external ophthalmoplegia with single large mitochondrial DNA deletion and neurogenic findings. ( 28175988 )
2017
7
Unilateral Ptosis and Homolateral Hemifacial Weakness in Chronic Progressive External Ophthalmoplegia. ( 28512510 )
2017
8
Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia. ( 28811105 )
2017
9
RE: "Unilateral Ptosis and Homolateral Hemifacial Weakness in Chronic Progressive External Ophthalmoplegia". ( 28533811 )
2017
10
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
11
Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. ( 29190634 )
2017
12
Surgical Technique for Pulled in Two Syndrome: Three Cases With Chronic Progressive External Ophthalmoplegia. ( 29156062 )
2017
13
Reply to "Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia". ( 28838816 )
2017
14
Nerve excitability changes related to muscle weakness in chronic progressive external ophthalmoplegia. ( 28535487 )
2017
15
Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort. ( 29246868 )
2017
16
A novel mitochondrial tRNA(Ala) gene variant causes chronic progressive external ophthalmoplegia in a patient with Huntington disease. ( 27014581 )
2016
17
Histopathological and genetic analysis of extraocular muscle in chronic progressive external ophthalmoplegia. ( 27470685 )
2016
18
Novel mutation in C10orf2 associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging. ( 26689116 )
2016
19
Multiple sclerosis and chronic progressive external ophthalmoplegia associated with a large scale mitochondrial DNA single deletion. ( 27113600 )
2016
20
Late-Onset Development of Eyelid Ptosis in Chronic Progressive External Ophthalmoplegia: A 30-Year Follow-up. ( 27928383 )
2016
21
Chronic Progressive External Ophthalmoplegia in the Absence of Ptosis. ( 27111092 )
2016
22
Vocal cord palsy in a case of chronic progressive external ophthalmoplegia. ( 26713034 )
2015
23
Pharyngeal transit in patients with chronic progressive external ophthalmoplegia. ( 25142449 )
2014
24
Cardiac involvement in chronic progressive external ophthalmoplegia. ( 25139213 )
2014
25
Novel mitochondrial tRNA(Ile) m.4282A>G gene mutation leads to chronic progressive external ophthalmoplegia plus phenotype. ( 25034047 )
2014
26
Chronic progressive external ophthalmoplegia with inflammatory myopathy. ( 25674260 )
2014
27
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
28
Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. ( 24727571 )
2014
29
No association between mitochondrial tRNA(Val) T1658C mutation and chronic progressive external ophthalmoplegia (CPEO). ( 23815321 )
2014
30
Autosomal dominant mutations in POLG and C10orf2: association with late onset chronic progressive external ophthalmoplegia and Parkinsonism in two patients. ( 23719791 )
2013
31
Extraocular muscle atrophy and central nervous system involvement in chronic progressive external ophthalmoplegia. ( 24086434 )
2013
32
Chronic progressive external ophthalmoplegia coexistent with motor neuron disease in a patient with a novel large-scale mitochondrial DNA deletion. ( 23266267 )
2013
33
Paralytic exophthalmos in chronic progressive external ophthalmoplegia. ( 22504268 )
2012
34
Sleep disturbances in chronic progressive external ophthalmoplegia. ( 21819490 )
2012
35
Diagnostic investigations of patients with chronic progressive external ophthalmoplegia. ( 23024221 )
2012
36
The mutations m.5628T>C and m.8348A>G in single muscle fibers of a patient with chronic progressive external ophthalmoplegia. ( 22743145 )
2012
37
Impairment of mitochondrial tRNAIle processing by a novel mutation associated with chronic progressive external ophthalmoplegia. ( 21292040 )
2011
38
Chronic progressive external ophthalmoplegia with T9957C mitochondrial DNA mutation in a Taiwanese patient. ( 21249588 )
2011
39
Multisystem disorder in late-onset chronic progressive external ophthalmoplegia. ( 21156440 )
2011
40
Esophageal contractions in patients with chronic progressive external ophthalmoplegia. ( 21399928 )
2011
41
Nature and frequency of respiratory involvement in chronic progressive external ophthalmoplegia. ( 21533826 )
2011
42
Disease impact in chronic progressive external ophthalmoplegia: more than meets the eye. ( 21236670 )
2011
43
A novel mitochondrial tRNA(Ile) point mutation associated with chronic progressive external ophthalmoplegia and hyperCKemia. ( 20884012 )
2011
44
Multiplex ligation-dependent probe amplification (MLPA) assay for the detection of mitochondrial DNA deletion in chronic progressive external ophthalmoplegia (CPEO). ( 22166510 )
2011
45
Morphological findings of extraocular myopathy with chronic progressive external ophthalmoplegia. ( 20192704 )
2010
46
Chronic progressive external ophthalmoplegia with recurrent quadriparesis : an unusual presentation. ( 21045517 )
2010
47
A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO). ( 20149659 )
2010
48
The management of strabismus in patients with chronic progressive external ophthalmoplegia. ( 20521878 )
2010
49
Eye movement recordings to investigate a supranuclear component in chronic progressive external ophthalmoplegia: a cross-sectional study. ( 20576783 )
2010
50
A novel mitochondrial tRNAGlu (MTTE) gene mutation causing chronic progressive external ophthalmoplegia at low levels of heteroplasmy in muscle. ( 20810132 )
2010

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

UniProtKB/Swiss-Prot genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:

75
# Symbol AA change Variation ID SNP ID
1 SLC25A4 p.Ala114Pro VAR_012111 rs104893873
2 SLC25A4 p.Val289Met VAR_012112 rs104893874
3 SLC25A4 p.Leu98Pro VAR_022459 rs104893876
4 SLC25A4 p.Asp104Gly VAR_022460 rs28999114
5 SLC25A4 p.Ala90Asp VAR_038814

ClinVar genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC25A4 NM_001151.3(SLC25A4): c.340G> C (p.Ala114Pro) single nucleotide variant Pathogenic rs104893873 GRCh37 Chromosome 4, 186066146: 186066146
2 SLC25A4 NM_001151.3(SLC25A4): c.340G> C (p.Ala114Pro) single nucleotide variant Pathogenic rs104893873 GRCh38 Chromosome 4, 185144992: 185144992
3 SLC25A4 NM_001151.3(SLC25A4): c.865G> A (p.Val289Met) single nucleotide variant Pathogenic rs104893874 GRCh37 Chromosome 4, 186068093: 186068093
4 SLC25A4 NM_001151.3(SLC25A4): c.865G> A (p.Val289Met) single nucleotide variant Pathogenic rs104893874 GRCh38 Chromosome 4, 185146939: 185146939
5 SLC25A4 NM_001151.3(SLC25A4): c.293T> C (p.Leu98Pro) single nucleotide variant Pathogenic rs104893876 GRCh37 Chromosome 4, 186066099: 186066099
6 SLC25A4 NM_001151.3(SLC25A4): c.293T> C (p.Leu98Pro) single nucleotide variant Pathogenic rs104893876 GRCh38 Chromosome 4, 185144945: 185144945
7 SLC25A4 NM_001151.3(SLC25A4): c.311A> G (p.Asp104Gly) single nucleotide variant Pathogenic rs28999114 GRCh37 Chromosome 4, 186066117: 186066117
8 SLC25A4 NM_001151.3(SLC25A4): c.311A> G (p.Asp104Gly) single nucleotide variant Pathogenic rs28999114 GRCh38 Chromosome 4, 185144963: 185144963

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 2.

Pathways for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

Sources for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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