PEOB2
MCID: PRG102
MIFTS: 29

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 2 (PEOB2)

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

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

MalaCards integrated aliases for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 2:

Name: Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 2 57 72 29 6
Peob2 57 12 72
Adult-Onset Chronic Progressive External Ophthalmoplegia with Mitochondrial Myopathy 12 58
Adult-Onset Cpeo with Mitochondrial Myopathy 12 58
Ophthalmoplegia, External, Progressive, with Mitochondrial Dna Deletions, Autosomal Recessive, Type 2 39
Autosomal Recessive Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 2 12
Progressive External Ophthalmoplegia, Autosomal Recessive 2 57
Autosomal Recessive Progressive External Ophthalmoplegia 2 12

Characteristics:

Orphanet epidemiological data:

58
adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy
Inheritance: Autosomal dominant,Mitochondrial inheritance; Age of onset: Adult;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
adult-onset (range early twenties to forties)
three unrelated families have been reported (last curated july 2015)


HPO:

31
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare otorhinolaryngological diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

OMIM® : 57 Autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-2 is a mitochondrial disorder characterized by adult onset of progressive external ophthalmoplegia, exercise intolerance, muscle weakness, and signs and symptoms of spinocerebellar ataxia, such as impaired gait and dysarthria. Some patients may have respiratory insufficiency. Laboratory studies are consistent with a defect in mtDNA replication (summary by Reyes et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive PEO, see PEOB1 (258450). (616479) (Updated 20-May-2021)

MalaCards based summary : Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 2, also known as peob2, is related to sensory ataxic neuropathy, dysarthria, and ophthalmoparesis and mitochondrial dna depletion syndrome 4a. An important gene associated with Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 2 is RNASEH1 (Ribonuclease H1). Affiliated tissues include eye and skeletal muscle, and related phenotypes are progressive external ophthalmoplegia and limb muscle weakness

Disease Ontology : 12 A chronic progressive external ophthalmoplegia characterized by adult onset of progressive external ophthalmoplegia, exercise intolerance, muscle weakness, and signs and symptoms of spinocerebellar ataxia that has material basis in homozygous or compound heterozygous mutation in RNASEH1 on chromosome 2p25.3.

UniProtKB/Swiss-Prot : 72 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2: A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB2 patients manifest exercise intolerance, muscle weakness, and signs and symptoms of spinocerebellar ataxia, such as impaired gait and dysarthria. Some patients may have respiratory insufficiency.

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

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

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

# Related Disease Score Top Affiliating Genes
1 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 9.7 RRM2B RNASEH1
2 mitochondrial dna depletion syndrome 4a 9.7 RRM2B RNASEH1
3 chronic progressive external ophthalmoplegia 9.6 RRM2B RNASEH1
4 mitochondrial myopathy 9.6 RRM2B RNASEH1
5 myopathy 9.5 RRM2B RNASEH1

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



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

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

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

58 31 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive external ophthalmoplegia 58 31 obligate (100%) Obligate (100%) HP:0000590
2 limb muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003690
3 exercise intolerance 58 31 hallmark (90%) Very frequent (99-80%) HP:0003546
4 dysarthria 58 31 frequent (33%) Frequent (79-30%) HP:0001260
5 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
6 high palate 58 31 frequent (33%) Frequent (79-30%) HP:0000218
7 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
8 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
9 respiratory insufficiency due to muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0002747
10 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
11 fatigable weakness of respiratory muscles 58 31 frequent (33%) Frequent (79-30%) HP:0030196
12 exercise-induced myalgia 58 31 frequent (33%) Frequent (79-30%) HP:0003738
13 difficulty climbing stairs 58 31 frequent (33%) Frequent (79-30%) HP:0003551
14 bilateral ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0001488
15 areflexia of lower limbs 58 31 frequent (33%) Frequent (79-30%) HP:0002522
16 weakness of facial musculature 58 31 frequent (33%) Frequent (79-30%) HP:0030319
17 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
18 abnormal pyramidal sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0007256
19 myalgia 58 31 occasional (7.5%) Frequent (79-30%) HP:0003326
20 gait imbalance 58 31 occasional (7.5%) Occasional (29-5%) HP:0002141
21 migraine 58 31 occasional (7.5%) Occasional (29-5%) HP:0002076
22 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
23 loss of ability to walk 58 31 occasional (7.5%) Occasional (29-5%) HP:0006957
24 pigmentary retinopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000580
25 abnormal atrioventricular conduction 58 31 occasional (7.5%) Occasional (29-5%) HP:0005150
26 psychomotor deterioration 58 31 occasional (7.5%) Occasional (29-5%) HP:0002361
27 esotropia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000565
28 sensorimotor neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0007141
29 neck flexor weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003722
30 deficit in phonologic short-term memory 58 31 occasional (7.5%) Occasional (29-5%) HP:0002549
31 limb dysmetria 58 31 occasional (7.5%) Occasional (29-5%) HP:0002406
32 abnormality of the spinocerebellar tracts 58 31 occasional (7.5%) Occasional (29-5%) HP:0003133
33 hyperreflexia 31 occasional (7.5%) HP:0001347
34 respiratory insufficiency 31 occasional (7.5%) HP:0002093
35 cognitive impairment 31 occasional (7.5%) HP:0100543
36 elevated serum creatine kinase 31 occasional (7.5%) HP:0003236
37 babinski sign 31 occasional (7.5%) HP:0003487
38 right bundle branch block 31 occasional (7.5%) HP:0011712
39 ptosis 31 HP:0000508
40 ataxia 31 HP:0001251
41 muscle weakness 31 HP:0001324
42 increased serum lactate 31 HP:0002151
43 external ophthalmoplegia 31 HP:0000544
44 cerebellar atrophy 31 HP:0001272
45 unsteady gait 31 HP:0002317
46 postural instability 31 HP:0002172

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
ptosis
external ophthalmoplegia, progressive

Voice:
dysarthria

Laboratory Abnormalities:
increased serum lactate
increased serum creatine kinase (in some patients)

Respiratory:
respiratory insufficiency (in some patients)

Neurologic Peripheral Nervous System:
sensorimotor demyelinating neuropathy, lower limbs (in some patients)

Neurologic Central Nervous System:
dysarthria
cerebellar atrophy
unsteady gait
postural instability
pyramidal signs
more
Abdomen Gastrointestinal:
dysphagia

Muscle Soft Tissue:
exercise intolerance
muscle atrophy
cox-negative fibers
ragged-red fibers seen on muscle biopsy
mitochondrial dna deletions
more
Cardiovascular Heart:
right bundle branch block (1 patient)

Clinical features from OMIM®:

616479 (Updated 20-May-2021)

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 2

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

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

# Genetic test Affiliating Genes
1 Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 2 29 RNASEH1

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

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

40
Eye, Skeletal Muscle

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

# Title Authors PMID Year
1
RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy. 6 57
26094573 2015

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RNASEH1 NM_002936.6(RNASEH1):c.469C>T (p.Arg157Ter) SNV Pathogenic 372198 rs373442996 GRCh37: 2:3598003-3598003
GRCh38: 2:3550413-3550413
2 RNASEH1 NM_002936.6(RNASEH1):c.554C>T (p.Ala185Val) SNV Pathogenic 372199 rs1057517675 GRCh37: 2:3596658-3596658
GRCh38: 2:3549068-3549068
3 RNASEH1 NM_002936.6(RNASEH1):c.424G>A (p.Val142Ile) SNV Likely pathogenic 372197 rs766294940 GRCh37: 2:3598048-3598048
GRCh38: 2:3550458-3550458

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

72
# Symbol AA change Variation ID SNP ID
1 RNASEH1 p.Val142Ile VAR_074561 rs766294940
2 RNASEH1 p.Ala185Val VAR_074562 rs105751767

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 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 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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