PEOB4
MCID: PRG128
MIFTS: 29

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4 (PEOB4)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Muscle 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 Recessive 4:

Name: Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4 56 73 29 6
Peob4 56 12 73
Adult-Onset Multiple Mitochondrial Dna Deletion Syndrome Due to Dguok Deficiency 12 58
Adult-Onset Multiple Mtdna Deletion Syndrome Due to Dguok Deficiency 12 58
Progressive External Ophthalmoplegia, Autosomal Recessive 4 56 73
Autosomal Recessive Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 4 12
Autosomal Recessive Progressive External Ophthalmoplegia 4 12

Characteristics:

Orphanet epidemiological data:

58
adult-onset multiple mitochondrial dna deletion syndrome due to dguok deficiency
Inheritance: Autosomal recessive; Age of onset: Adult;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in adulthood
variable presentation and phenotype


HPO:

31
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 4:
Inheritance autosomal recessive inheritance
Onset and clinical course adult onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

OMIM : 56 Autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4) is an autosomal recessive disorder characterized by adult onset of eye muscle weakness and proximal limb muscle weakness associated with deletions of mtDNA on skeletal muscle biopsy, which results from defective mtDNA replication in post-mitotic muscle tissue. Additional features are more variable (summary by Ronchi et al., 2012). For a discussion of genetic heterogeneity of autosomal recessive PEO, see PEOB1 (258450). (617070)

MalaCards based summary : Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4, is also known as peob4. An important gene associated with Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4 is DGUOK (Deoxyguanosine Kinase). Affiliated tissues include eye, skeletal muscle and liver, and related phenotypes are dysphagia and sensory axonal neuropathy

Disease Ontology : 12 A chronic progressive external ophthalmoplegia characterized by adult onset of eye muscle weakness and proximal limb muscle weakness that has material basis in homozygous or compound heterozygous mutation in DGUOK on chromosome 2p13.1.

UniProtKB/Swiss-Prot : 73 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4: A form of progressive external ophthalmoplegia, a mitochondrial myopathy characterized by progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. PEOB4 patients manifest clinically variable features including mitochondrial myopathy with or without progressive external ophthalmoplegia, recurrent rhabdomyolysis, and adult-onset lower motor neuron syndrome with mild cognitive impairment.

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

Human phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4:

58 31 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 58 31 occasional (7.5%) Frequent (79-30%) HP:0002015
2 sensory axonal neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0003390
3 progressive external ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000590
4 bilateral ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0001488
5 lower limb muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0007340
6 adult onset sensorineural hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0008615
7 limb-girdle muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003797
8 depressivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000716
9 ataxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001251
10 dysphonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001618
11 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
12 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
13 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
14 myalgia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003326
15 pelvic girdle muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003749
16 dementia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000726
17 asthenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0025406
18 viral infection-induced rhabdomyolysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003558
19 muscle spasm 31 occasional (7.5%) HP:0003394
20 cognitive impairment 58 31 Occasional (29-5%) HP:0100543
21 ptosis 31 HP:0000508
22 cerebral cortical atrophy 31 HP:0002120
23 sensorineural hearing impairment 31 HP:0000407
24 skeletal muscle atrophy 31 HP:0003202
25 increased serum lactate 31 HP:0002151
26 ragged-red muscle fibers 31 HP:0003200
27 mitochondrial myopathy 31 HP:0003737
28 muscle cramps 58 Occasional (29-5%)
29 hyporeflexia 31 HP:0001265
30 proximal muscle weakness 31 HP:0003701
31 limb-girdle muscle weakness 58 Frequent (79-30%)
32 peripheral axonal neuropathy 31 HP:0003477
33 distal muscle weakness 31 HP:0002460
34 elevated serum creatine kinase 31 HP:0003236

Symptoms via clinical synopsis from OMIM:

56
Voice:
dysphonia

Abdomen Gastrointestinal:
dysphagia (in some patients)

Laboratory Abnormalities:
increased serum lactate, mild
increased serum creatine kinase, mild

Head And Neck Ears:
sensorineural deafness (family a)

Muscle Soft Tissue:
mitochondrial myopathy
muscle atrophy
muscle weakness, proximal
cox-negative fibers
myopathic changes seen on emg
more
Neurologic Peripheral Nervous System:
hyporeflexia (family a)
axonal neuropathy (family a)

Neurologic Central Nervous System:
cortical atrophy (family a)
cognitive impairment (family a)

Head And Neck Eyes:
progressive external ophthalmoplegia (in most patients)
ptosis (in most patients)

Clinical features from OMIM:

617070

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 4

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

Genetic tests related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4:

# Genetic test Affiliating Genes
1 Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4 29 DGUOK

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

MalaCards organs/tissues related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4:

40
Eye, Skeletal Muscle, Liver

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Articles related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4:

# Title Authors PMID Year
1
Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions. 56 6
23043144 2012
2
Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension. 6
26874653 2016
3
Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia. 6
21951382 2011
4
RRM2B mutations are frequent in familial PEO with multiple mtDNA deletions. 6
21646632 2011
5
Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain deficiency in childhood. 6
17452231 2007
6
Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion. 6
17073823 2007
7
Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion. 6
11983456 2002

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

ClinVar genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DGUOK NM_080916.3(DGUOK):c.591G>A (p.Gln197=)SNV Pathogenic 214286 rs748597500 2:74177859-74177859 2:73950732-73950732
2 DGUOK NM_080916.3(DGUOK):c.603_604GA[1] (p.Arg202fs)short repeat Pathogenic 214288 rs863223949 2:74184265-74184266 2:73957138-73957139
3 DGUOK NM_080916.3(DGUOK):c.130G>A (p.Glu44Lys)SNV Pathogenic 253066 rs762550967 2:74154167-74154167 2:73927040-73927040
4 DGUOK NM_080916.3(DGUOK):c.186C>A (p.Tyr62Ter)SNV Pathogenic 253068 rs879255617 2:74166080-74166080 2:73938953-73938953
5 DGUOK NM_080916.3(DGUOK):c.444-11C>GSNV Pathogenic/Likely pathogenic 253069 rs536746349 2:74177701-74177701 2:73950574-73950574
6 DGUOK NM_080916.3(DGUOK):c.137A>G (p.Asn46Ser)SNV Pathogenic/Likely pathogenic 253062 rs763615602 2:74154174-74154174 2:73927047-73927047
7 DGUOK NM_080916.3(DGUOK):c.462T>A (p.Asn154Lys)SNV Conflicting interpretations of pathogenicity 214285 rs144181978 2:74177730-74177730 2:73950603-73950603
8 DGUOK NM_080916.3(DGUOK):c.155C>G (p.Ser52Cys)SNV Uncertain significance 638350 2:74166049-74166049 2:73938922-73938922
9 DGUOK NM_080916.3(DGUOK):c.509A>G (p.Gln170Arg)SNV Benign 137082 rs74874677 2:74177777-74177777 2:73950650-73950650

UniProtKB/Swiss-Prot genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Recessive 4:

73
# Symbol AA change Variation ID SNP ID
1 DGUOK p.Glu44Lys VAR_076979 rs762550967
2 DGUOK p.Asn154Lys VAR_076981 rs144181978

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 4.

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...

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