MCID: PRG131
MIFTS: 35

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 1

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

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

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

Name: Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 1 57
Cerebellar Ataxia Infantile with Progressive External Ophthalmoplegia 53 29 6
Progressive External Ophthalmoplegia, Autosomal Recessive 1 57 53
Autosomal Recessive Progressive External Ophthalmoplegia 53 59
Chronic Progressive External Ophthalmoplegia 75 73
Peob1 57 75
Arpeo 53 59
Ophthalmoplegia, External, Progressive, with Mitochondrial Dna Deletions, Autosomal Recessive, Type 1 40
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive, 1 75
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 73
Progressive External Ophthalmoplegia with Cerebellar Ataxia Infantile 53
Progressive External Ophthalmoplegia, Autosomal Recessive 13
Progressive External Ophthalmoplegia Autosomal Recessive 75
Ocular Myopathy of Von Graefe-Fuchs 75
Mitochondrial Ocular Myopathy 75
Kearns-Sayre Syndrome 73
Graefe Disease 75
Cpeo 75

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive progressive external ophthalmoplegia
Inheritance: Autosomal recessive; Age of onset: All ages;

OMIM:

57
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 with mitochondrial dna deletions, autosomal recessive 1:
Onset and clinical course adult onset phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

OMIM : 57 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 with Mitochondrial Dna Deletions, Autosomal Recessive 1, also known as cerebellar ataxia infantile with progressive external ophthalmoplegia, 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 Recessive 1 is POLG (DNA Polymerase Gamma, Catalytic Subunit). Affiliated tissues include skeletal muscle and eye, and related phenotypes are visual impairment and ptosis

UniProtKB/Swiss-Prot : 75 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 with Mitochondrial Dna...

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



Diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 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)
optic atrophy (1 patient)
dyschromatopsia (1 patient)
poor vision (1 patient)

Abdomen Gastrointestinal:
dysphagia

Neurologic Central Nervous System:
gait ataxia
limb ataxia
rigidity
bradykinesia
parkinsonism
more
Neurologic Peripheral Nervous System:
sensory axonal neuropathy
areflexia
hyporeflexia
sensory ataxic neuropathy
decreased sensory nerve action potentials
more
Laboratory Abnormalities:
increased csf protein
mildly increased creatine kinase

Muscle Soft Tissue:
dysarthria
dysphonia
exercise intolerance
ragged red fibers seen on muscle biopsy
muscle weakness, proximal
more
Respiratory:
respiratory insufficiency due to muscle weakness

Skeletal Feet:
pes cavus
'clawed' toes

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

Neurologic Behavioral Psychiatric Manifestations:
depression
emotional instability


Clinical features from OMIM:

258450

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

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

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


cerebellar ataxia, seizures, muscle weakness, ophthalmoplegia

MGI Mouse Phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.62 POLG TK2

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

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

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

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

# Genetic test Affiliating Genes
1 Cerebellar Ataxia Infantile with Progressive External Ophthalmoplegia 29 POLG

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

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

41
Skeletal Muscle, Eye

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

# Title Authors Year
1
Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions. ( 21937588 )
2012
2
Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia. ( 21951382 )
2011

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

75 (show all 32)
# 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 with Mitochondrial Dna Deletions, Autosomal Recessive 1:

6
(show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic rs113994095 GRCh37 Chromosome 15, 89870432: 89870432
2 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic rs113994095 GRCh38 Chromosome 15, 89327201: 89327201
3 POLG NM_002693.2(POLG): c.911T> G (p.Leu304Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918044 GRCh37 Chromosome 15, 89872286: 89872286
4 POLG NM_002693.2(POLG): c.911T> G (p.Leu304Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918044 GRCh38 Chromosome 15, 89329055: 89329055
5 POLG NM_002693.2(POLG): c.8G> C (p.Arg3Pro) single nucleotide variant Pathogenic rs121918045 GRCh37 Chromosome 15, 89876978: 89876978
6 POLG NM_002693.2(POLG): c.8G> C (p.Arg3Pro) single nucleotide variant Pathogenic rs121918045 GRCh38 Chromosome 15, 89333747: 89333747
7 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh37 Chromosome 15, 89865023: 89865023
8 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh38 Chromosome 15, 89321792: 89321792
9 POLG NM_002693.2(POLG): c.2209G> C (p.Gly737Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918054 GRCh37 Chromosome 15, 89866691: 89866691
10 POLG NM_002693.2(POLG): c.2209G> C (p.Gly737Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918054 GRCh38 Chromosome 15, 89323460: 89323460
11 POLG NM_002693.2(POLG): c.32G> A (p.Gly11Asp) single nucleotide variant Uncertain significance rs765472726 GRCh37 Chromosome 15, 89876954: 89876954
12 POLG NM_002693.2(POLG): c.32G> A (p.Gly11Asp) single nucleotide variant Uncertain significance rs765472726 GRCh38 Chromosome 15, 89333723: 89333723
13 POLG NM_002693.2(POLG): c.1174C> G (p.Leu392Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145289229 GRCh37 Chromosome 15, 89871763: 89871763
14 POLG NM_002693.2(POLG): c.1174C> G (p.Leu392Val) single nucleotide variant Conflicting interpretations of pathogenicity rs145289229 GRCh38 Chromosome 15, 89328532: 89328532
15 POLG NM_002693.2(POLG): c.2554C> T (p.Arg852Cys) single nucleotide variant Pathogenic rs144500145 GRCh37 Chromosome 15, 89865011: 89865011
16 POLG NM_002693.2(POLG): c.2554C> T (p.Arg852Cys) single nucleotide variant Pathogenic rs144500145 GRCh38 Chromosome 15, 89321780: 89321780
17 POLG NM_002693.2(POLG): c.2207A> G (p.Asn736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs138457939 GRCh38 Chromosome 15, 89323462: 89323462
18 POLG NM_002693.2(POLG): c.2207A> G (p.Asn736Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs138457939 GRCh37 Chromosome 15, 89866693: 89866693
19 POLG NM_002693.2(POLG): c.2419C> T (p.Arg807Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs769827124 GRCh37 Chromosome 15, 89865980: 89865980
20 POLG NM_002693.2(POLG): c.2419C> T (p.Arg807Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs769827124 GRCh38 Chromosome 15, 89322749: 89322749
21 POLG NM_002693.2(POLG): c.3612_3613insAACT (p.Gly1205Asnfs) insertion Pathogenic rs886043241 GRCh37 Chromosome 15, 89860637: 89860638
22 POLG NM_002693.2(POLG): c.3612_3613insAACT (p.Gly1205Asnfs) insertion Pathogenic rs886043241 GRCh38 Chromosome 15, 89317406: 89317407

Expression for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Search GEO for disease gene expression data for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 1.

Pathways for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

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

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

Sources for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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