MCID: PRG104
MIFTS: 36

Progressive External Ophthalmoplegia, Autosomal Recessive 1

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Eye diseases, Muscle diseases

Aliases & Classifications for Progressive External Ophthalmoplegia, Autosomal Recessive 1

MalaCards integrated aliases for Progressive External Ophthalmoplegia, Autosomal Recessive 1:

Name: Progressive External Ophthalmoplegia, Autosomal Recessive 1 54 50
Autosomal Recessive Progressive External Ophthalmoplegia 50 24 56
Cerebellar Ataxia Infantile with Progressive External Ophthalmoplegia 50 29
Chronic Progressive External Ophthalmoplegia 71 69
Arpeo 50 56
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive, 1 71
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 69
Progressive External Ophthalmoplegia with Cerebellar Ataxia Infantile 50
Progressive External Ophthalmoplegia, Autosomal Recessive 13
Progressive External Ophthalmoplegia Autosomal Recessive 71
Ocular Myopathy of Von Graefe-Fuchs 71
Mitochondrial Ocular Myopathy 71
Kearns-Sayre Syndrome 69
Graefe Disease 71
Peob1 71
Cpeo 71

Characteristics:

Orphanet epidemiological data:

56
autosomal recessive progressive external ophthalmoplegia
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in late teens to twenties
peo is not always present
sando is a phenotypic variant of autosomal recessive peo
see also autosomal dominant peoa1


HPO:

32
progressive external ophthalmoplegia, autosomal recessive 1:
Onset and clinical course phenotypic variability adult onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Progressive External Ophthalmoplegia, Autosomal Recessive 1

OMIM : 54
Progressive external ophthalmoplegia (PEO) is characterized by multiple mitochondrial DNA (mtDNA) 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. Less common features include mitral valve prolapse, cardiomyopathy, and gastrointestinal dysmotility. Both autosomal dominant and autosomal recessive inheritance can occur; autosomal recessive inheritance is usually more severe (Filosto et al., 2003; Luoma et al., 2004). Drachman (1975) gave a classification of disorders associated with progressive external ophthalmoplegia, which he termed 'ophthalmoplegia plus' (Drachman, 1968). (258450)

MalaCards based summary : Progressive External Ophthalmoplegia, Autosomal Recessive 1, also known as autosomal recessive progressive external ophthalmoplegia, is related to chronic progressive external ophthalmoplegia and kearns-sayre syndrome, and has symptoms including visual impairment, optic atrophy and dysphagia. An important gene associated with Progressive External Ophthalmoplegia, Autosomal Recessive 1 is POLG (DNA Polymerase Gamma, Catalytic Subunit). Affiliated tissues include skeletal muscle and eye, and related phenotype is adipose tissue.

UniProtKB/Swiss-Prot : 71 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive, 1: A severe form of progressive external ophthalmoplegia, a disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. It is clinically more heterogeneous than the autosomal dominant forms.

Related Diseases for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Graphical network of the top 20 diseases related to Progressive External Ophthalmoplegia, Autosomal Recessive 1:



Diseases related to Progressive External Ophthalmoplegia, Autosomal Recessive 1

Symptoms & Phenotypes for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Symptoms via clinical synopsis from OMIM:

54

Muscle Soft Tissue:
facial weakness
dysarthria
muscle weakness, proximal
exercise intolerance
emg shows myopathic changes
more
Neurologic- Peripheral Nervous System:
hyporeflexia
areflexia
decreased sensory nerve action potentials
sensory axonal neuropathy
sensory ataxic neuropathy
more
Neurologic- Central Nervous System:
parkinsonism
bradykinesia
rigidity
gait ataxia
limb ataxia
more
Skeletal- Feet:
pes cavus
'clawed' toes

Cardiovascular- Heart:
cardiomyopathy (in some patients)
mitral valve prolapse
mitral insufficiency

Abdomen- Gastroin testinal:
dysphagia

Head And Neck- Eyes:
ptosis
external ophthalmoplegia, progressive (peo)
optic atrophy (1 patient)
poor vision (1 patient)
dyschromatopsia (1 patient)

Neurologic- Behavioral Psychiatric Manifestations:
depression
emotional instability

Respiratory:
respiratory insufficiency due to muscle weakness

Laboratory- Abnormalities:
increased csf protein
mildly increased creatine kinase


Clinical features from OMIM:

258450

Human phenotypes related to Progressive External Ophthalmoplegia, Autosomal Recessive 1:

32 (show all 44)
id Description HPO Frequency HPO Source Accession
1 visual impairment 32 occasional (7.5%) HP:0000505
2 optic atrophy 32 occasional (7.5%) HP:0000648
3 dysphagia 32 HP:0002015
4 dysarthria 32 HP:0001260
5 hyporeflexia 32 HP:0001265
6 ptosis 32 HP:0000508
7 emotional lability 32 HP:0000712
8 exercise intolerance 32 HP:0003546
9 parkinsonism 32 HP:0001300
10 bradykinesia 32 HP:0002067
11 rigidity 32 HP:0002063
12 depression 32 HP:0000716
13 pes cavus 32 HP:0001761
14 areflexia 32 HP:0001284
15 cardiomyopathy 32 occasional (7.5%) HP:0001638
16 gait ataxia 32 HP:0002066
17 limb ataxia 32 HP:0002070
18 respiratory insufficiency due to muscle weakness 32 HP:0002747
19 generalized amyotrophy 32 HP:0003700
20 increased csf protein 32 HP:0002922
21 steppage gait 32 HP:0003376
22 distal muscle weakness 32 HP:0002460
23 positive romberg sign 32 HP:0002403
24 mitral valve prolapse 32 HP:0001634
25 proximal muscle weakness 32 HP:0003701
26 mitochondrial myopathy 32 HP:0003737
27 dysphonia 32 HP:0001618
28 muscle fiber necrosis 32 HP:0003713
29 dyschromatopsia 32 occasional (7.5%) HP:0007641
30 facial palsy 32 HP:0010628
31 mitral regurgitation 32 HP:0001653
32 progressive external ophthalmoplegia 32 HP:0000590
33 sensory axonal neuropathy 32 HP:0003390
34 sensory ataxic neuropathy 32 HP:0003434
35 elevated serum creatine phosphokinase 32 HP:0003236
36 ragged-red muscle fibers 32 HP:0003200
37 mildly elevated creatine phosphokinase 32 HP:0008180
38 increased variability in muscle fiber diameter 32 HP:0003557
39 emg 32 HP:0003458
40 subsarcolemmal accumulations of abnormally shaped mitochondria 32 HP:0003548
41 cytochrome c oxidase-negative muscle fibers 32 HP:0003688
42 multiple mitochondrial dna deletions 32 HP:0003689
43 impaired distal proprioception 32 HP:0006858
44 impaired distal vibration sensation 32 HP:0006886

UMLS symptoms related to Progressive External Ophthalmoplegia, Autosomal Recessive 1:


cerebellar ataxia, seizures, muscle weakness, ophthalmoplegia

MGI Mouse Phenotypes related to Progressive External Ophthalmoplegia, Autosomal Recessive 1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.62 POLG TK2

Drugs & Therapeutics for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Search Clinical Trials , NIH Clinical Center for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Genetic Tests for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Genetic tests related to Progressive External Ophthalmoplegia, Autosomal Recessive 1:

id Genetic test Affiliating Genes
1 Cerebellar Ataxia Infantile with Progressive External Ophthalmoplegia 29
2 Autosomal Recessive Progressive External Ophthalmoplegia 24 POLG

Anatomical Context for Progressive External Ophthalmoplegia, Autosomal Recessive 1

MalaCards organs/tissues related to Progressive External Ophthalmoplegia, Autosomal Recessive 1:

39
Skeletal Muscle, Eye

Publications for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Variations for Progressive External Ophthalmoplegia, Autosomal Recessive 1

UniProtKB/Swiss-Prot genetic disease variations for Progressive External Ophthalmoplegia, Autosomal Recessive 1:

71 (show all 32)
id Symbol AA change Variation ID SNP ID
1 POLG p.Arg3Pro VAR_012153 rs121918045
2 POLG p.Leu304Arg VAR_012154 rs121918044
3 POLG p.Ala467Thr VAR_012155 rs113994095
4 POLG p.Arg1146Cys VAR_014910 rs2307440
5 POLG p.Arg227Trp VAR_023663 rs121918056
6 POLG p.Thr251Ile VAR_023664 rs113994094
7 POLG p.Arg309Leu VAR_023665
8 POLG p.Trp312Arg VAR_023666
9 POLG p.Gly431Val VAR_023667
10 POLG p.Asn468Asp VAR_023668 rs145843073
11 POLG p.Arg579Trp VAR_023670 rs556925652
12 POLG p.Pro587Leu VAR_023671 rs113994096
13 POLG p.Gly848Ser VAR_023675 rs113994098
14 POLG p.Ala889Thr VAR_023677 rs763393580
15 POLG p.His932Tyr VAR_023679 rs121918048
16 POLG p.Arg1047Gln VAR_023683 rs768028281
17 POLG p.Gly1076Val VAR_023685
18 POLG p.Arg1096Cys VAR_023686 rs201732356
19 POLG p.Ser1104Cys VAR_023687
20 POLG p.Ala1105Thr VAR_023688 rs753410045
21 POLG p.Val1106Ile VAR_023689
22 POLG p.Gly268Ala VAR_058873 rs61752784
23 POLG p.Gln308His VAR_058875 rs745539599
24 POLG p.Gly380Asp VAR_058876
25 POLG p.Arg562Gln VAR_058880 rs781168350
26 POLG p.Arg574Trp VAR_058881 rs774474723
27 POLG p.Met603Leu VAR_058882
28 POLG p.Pro648Arg VAR_058884 rs796052906
29 POLG p.Gly737Arg VAR_058885 rs121918054
30 POLG p.Arg807Pro VAR_058888
31 POLG p.Arg853Trp VAR_058889 rs121918053
32 POLG p.Asp1184Asn VAR_058897

ClinVar genetic disease variations for Progressive External Ophthalmoplegia, Autosomal Recessive 1:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic/Likely pathogenic rs113994095 GRCh37 Chromosome 15, 89870432: 89870432
2 POLG NM_002693.2(POLG): c.911T> G (p.Leu304Arg) single nucleotide variant Pathogenic rs121918044 GRCh37 Chromosome 15, 89872286: 89872286
3 POLG NM_002693.2(POLG): c.8G> C (p.Arg3Pro) single nucleotide variant Pathogenic rs121918045 GRCh37 Chromosome 15, 89876978: 89876978
4 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh37 Chromosome 15, 89865023: 89865023
5 POLG NM_002693.2(POLG): c.2557C> T (p.Arg853Trp) single nucleotide variant Pathogenic rs121918053 GRCh37 Chromosome 15, 89865008: 89865008
6 POLG NM_002693.2(POLG): c.2554C> T (p.Arg852Cys) single nucleotide variant Pathogenic rs144500145 GRCh37 Chromosome 15, 89865011: 89865011
7 POLG NM_002693.2(POLG): c.3612_3613insAACT (p.Gly1205Asnfs) insertion Pathogenic rs886043241 GRCh37 Chromosome 15, 89860637: 89860638

Expression for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Search GEO for disease gene expression data for Progressive External Ophthalmoplegia, Autosomal Recessive 1.

Pathways for Progressive External Ophthalmoplegia, Autosomal Recessive 1

GO Terms for Progressive External Ophthalmoplegia, Autosomal Recessive 1

Biological processes related to Progressive External Ophthalmoplegia, Autosomal Recessive 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 DNA biosynthetic process GO:0071897 8.62 POLG TK2

Sources for Progressive External Ophthalmoplegia, Autosomal Recessive 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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