PEOB4
MCID: PRG128
MIFTS: 26

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

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic 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 58 76 30 6
Progressive External Ophthalmoplegia, Autosomal Recessive 4 58 76
Peob4 58 76
Adult-Onset Multiple Mitochondrial Dna Deletion Syndrome Due to Dguok Deficiency 60
Adult-Onset Multiple Mtdna Deletion Syndrome Due to Dguok Deficiency 60

Characteristics:

Orphanet epidemiological data:

60
adult-onset multiple mitochondrial dna deletion syndrome due to dguok deficiency
Inheritance: Autosomal recessive; Age of onset: Adult;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in adulthood
variable presentation and phenotype


HPO:

33
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 4:
Onset and clinical course adult onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

OMIM : 58 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 progressive external ophthalmoplegia, autosomal recessive 4. 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 bone, and related phenotypes are dysphagia and sensory axonal neuropathy

UniProtKB/Swiss-Prot : 76 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:

60 33 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 60 33 occasional (7.5%) Frequent (79-30%) HP:0002015
2 sensory axonal neuropathy 60 33 frequent (33%) Frequent (79-30%) HP:0003390
3 progressive external ophthalmoplegia 60 33 frequent (33%) Frequent (79-30%) HP:0000590
4 lower limb muscle weakness 60 33 frequent (33%) Frequent (79-30%) HP:0007340
5 bilateral ptosis 60 33 frequent (33%) Frequent (79-30%) HP:0001488
6 adult onset sensorineural hearing impairment 60 33 frequent (33%) Frequent (79-30%) HP:0008615
7 limb-girdle muscle atrophy 60 33 frequent (33%) Frequent (79-30%) HP:0003797
8 depressivity 60 33 occasional (7.5%) Occasional (29-5%) HP:0000716
9 ataxia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001251
10 dysphonia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001618
11 cataract 60 33 occasional (7.5%) Occasional (29-5%) HP:0000518
12 optic atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0000648
13 strabismus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000486
14 myalgia 60 33 occasional (7.5%) Occasional (29-5%) HP:0003326
15 pelvic girdle muscle weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0003749
16 dementia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000726
17 asthenia 60 33 occasional (7.5%) Occasional (29-5%) HP:0025406
18 viral infection-induced rhabdomyolysis 60 33 occasional (7.5%) Occasional (29-5%) HP:0003558
19 muscle spasm 33 occasional (7.5%) HP:0003394
20 cognitive impairment 60 33 Occasional (29-5%) HP:0100543
21 ptosis 33 HP:0000508
22 sensorineural hearing impairment 33 HP:0000407
23 skeletal muscle atrophy 33 HP:0003202
24 cerebral cortical atrophy 33 HP:0002120
25 increased serum lactate 33 HP:0002151
26 ragged-red muscle fibers 33 HP:0003200
27 mitochondrial myopathy 33 HP:0003737
28 muscle cramps 60 Occasional (29-5%)
29 hyporeflexia 33 HP:0001265
30 proximal muscle weakness 33 HP:0003701
31 limb-girdle muscle weakness 60 Frequent (79-30%)
32 peripheral axonal neuropathy 33 HP:0003477
33 distal muscle weakness 33 HP:0002460
34 elevated serum creatine kinase 33 HP:0003236

Symptoms via clinical synopsis from OMIM:

58
Voice:
dysphonia

Abdomen Gastrointestinal:
dysphagia (in some patients)

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

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

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)

Head And Neck Ears:
sensorineural deafness (family a)

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

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 30 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:

42
Eye, Skeletal Muscle, Bone

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

# Title Authors Year
1
Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions. ( 23043144 )
2012
2
Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain deficiency in childhood. ( 17452231 )
2007
3
Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion. ( 17073823 )
2007
4
Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion. ( 11983456 )
2002

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

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

76
# Symbol AA change Variation ID SNP ID
1 DGUOK p.Glu44Lys VAR_076979 rs762550967
2 DGUOK p.Asn154Lys VAR_076981 rs144181978

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

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 DGUOK NM_080916.2(DGUOK): c.509A> G (p.Gln170Arg) single nucleotide variant Benign rs74874677 GRCh37 Chromosome 2, 74177777: 74177777
2 DGUOK NM_080916.2(DGUOK): c.509A> G (p.Gln170Arg) single nucleotide variant Benign rs74874677 GRCh38 Chromosome 2, 73950650: 73950650
3 DGUOK NM_080916.2(DGUOK): c.462T> A (p.Asn154Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs144181978 GRCh38 Chromosome 2, 73950603: 73950603
4 DGUOK NM_080916.2(DGUOK): c.462T> A (p.Asn154Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs144181978 GRCh37 Chromosome 2, 74177730: 74177730
5 DGUOK NM_080916.1(DGUOK): c.591G> A (p.Gln197=) single nucleotide variant Pathogenic rs748597500 GRCh38 Chromosome 2, 73950732: 73950732
6 DGUOK NM_080916.1(DGUOK): c.591G> A (p.Gln197=) single nucleotide variant Pathogenic rs748597500 GRCh37 Chromosome 2, 74177859: 74177859
7 DGUOK NM_080916.1(DGUOK): c.605_606delGA (p.Arg202Thrfs) deletion Pathogenic rs863223949 GRCh38 Chromosome 2, 73957138: 73957139
8 DGUOK NM_080916.1(DGUOK): c.605_606delGA (p.Arg202Thrfs) deletion Pathogenic rs863223949 GRCh37 Chromosome 2, 74184265: 74184266
9 DGUOK NM_080916.2(DGUOK): c.137A> G (p.Asn46Ser) single nucleotide variant Pathogenic/Likely pathogenic rs763615602 GRCh37 Chromosome 2, 74154174: 74154174
10 DGUOK NM_080916.2(DGUOK): c.137A> G (p.Asn46Ser) single nucleotide variant Pathogenic/Likely pathogenic rs763615602 GRCh38 Chromosome 2, 73927047: 73927047
11 DGUOK NM_080916.2(DGUOK): c.130G> A (p.Glu44Lys) single nucleotide variant Pathogenic rs762550967 GRCh37 Chromosome 2, 74154167: 74154167
12 DGUOK NM_080916.2(DGUOK): c.130G> A (p.Glu44Lys) single nucleotide variant Pathogenic rs762550967 GRCh38 Chromosome 2, 73927040: 73927040
13 DGUOK NM_080916.2(DGUOK): c.186C> A (p.Tyr62Ter) single nucleotide variant Pathogenic rs879255617 GRCh37 Chromosome 2, 74166080: 74166080
14 DGUOK NM_080916.2(DGUOK): c.186C> A (p.Tyr62Ter) single nucleotide variant Pathogenic rs879255617 GRCh38 Chromosome 2, 73938953: 73938953
15 DGUOK NM_080916.1(DGUOK): c.444-11C> G single nucleotide variant Pathogenic/Likely pathogenic rs536746349 GRCh38 Chromosome 2, 73950574: 73950574
16 DGUOK NM_080916.1(DGUOK): c.444-11C> G single nucleotide variant Pathogenic/Likely pathogenic rs536746349 GRCh37 Chromosome 2, 74177701: 74177701

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...

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