MCID: PRG038
MIFTS: 36

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 2

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 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 cerebellar ataxia, seizures and muscle weakness. 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 skeletal muscle, eye and retina, and related phenotypes are sensorineural hearing impairment and ptosis

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

(show all 42)
# Related Disease Score Top Affiliating Genes
1 chronic progressive external ophthalmoplegia 12.7
2 kearns-sayre syndrome 12.1
3 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1 11.8
4 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3 11.8
5 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 4 11.8
6 maternally-inherited progressive external ophthalmoplegia 11.6
7 strabismus 11.4
8 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 1 11.4
9 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2 11.2
10 ocular muscular dystrophy 11.2
11 ptosis 10.3
12 myopathy 10.3
13 mitochondrial myopathy 10.1
14 optic nerve disease 10.1
15 neuropathy 10.1
16 multiple sclerosis 10.0
17 polyglucosan body myopathy 1 with or without immunodeficiency 10.0
18 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
19 retinitis 10.0
20 mitochondrial metabolism disease 10.0
21 mitochondrial disorders 10.0
22 atrial standstill 1 9.8
23 huntington disease 9.8
24 hypercholesterolemia, familial 9.8
25 macular dystrophy, dominant cystoid 9.8
26 retinitis pigmentosa 9.8
27 aging 9.8
28 focal segmental glomerulosclerosis 1 9.8
29 leber congenital amaurosis 4 9.8
30 focal segmental glomerulosclerosis 9.8
31 keratopathy 9.8
32 motor neuron disease 9.8
33 atrioventricular block 9.8
34 third-degree atrioventricular block 9.8
35 sensorineural hearing loss 9.8
36 esophagitis 9.8
37 pharyngitis 9.8
38 macular retinal edema 9.8
39 intracranial hypotension 9.8
40 neuronitis 9.8
41 exophthalmos 9.8
42 encephalopathy 9.8

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

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


cerebellar ataxia, seizures, muscle weakness, ophthalmoplegia, 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
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 2:

(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 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...

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