PEOB4
MCID: PRG128
MIFTS: 27

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 57 74 29 6
Progressive External Ophthalmoplegia, Autosomal Recessive 4 57 74
Peob4 57 74
Adult-Onset Multiple Mitochondrial Dna Deletion Syndrome Due to Dguok Deficiency 59
Adult-Onset Multiple Mtdna Deletion Syndrome Due to Dguok Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
adult-onset multiple mitochondrial dna deletion syndrome due to dguok deficiency
Inheritance: Autosomal recessive; Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in adulthood
variable presentation and phenotype


HPO:

32
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 4:
Inheritance autosomal recessive inheritance
Onset and clinical course adult onset


Classifications:



External Ids:

MeSH 44 D017246
ICD10 via Orphanet 34 G71.3
Orphanet 59 ORPHA329314

Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

OMIM : 57 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 skeletal muscle, eye and liver, and related phenotypes are dysphagia and sensory axonal neuropathy

UniProtKB/Swiss-Prot : 74 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:

59 32 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 59 32 occasional (7.5%) Frequent (79-30%) HP:0002015
2 sensory axonal neuropathy 59 32 frequent (33%) Frequent (79-30%) HP:0003390
3 progressive external ophthalmoplegia 59 32 frequent (33%) Frequent (79-30%) HP:0000590
4 lower limb muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0007340
5 bilateral ptosis 59 32 frequent (33%) Frequent (79-30%) HP:0001488
6 adult onset sensorineural hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0008615
7 limb-girdle muscle atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003797
8 depressivity 59 32 occasional (7.5%) Occasional (29-5%) HP:0000716
9 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
10 dysphonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001618
11 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
12 optic atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000648
13 strabismus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000486
14 myalgia 59 32 occasional (7.5%) Occasional (29-5%) HP:0003326
15 pelvic girdle muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0003749
16 dementia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000726
17 asthenia 59 32 occasional (7.5%) Occasional (29-5%) HP:0025406
18 viral infection-induced rhabdomyolysis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003558
19 muscle spasm 32 occasional (7.5%) HP:0003394
20 cognitive impairment 59 32 Occasional (29-5%) HP:0100543
21 ptosis 32 HP:0000508
22 sensorineural hearing impairment 32 HP:0000407
23 skeletal muscle atrophy 32 HP:0003202
24 cerebral cortical atrophy 32 HP:0002120
25 increased serum lactate 32 HP:0002151
26 ragged-red muscle fibers 32 HP:0003200
27 mitochondrial myopathy 32 HP:0003737
28 muscle cramps 59 Occasional (29-5%)
29 hyporeflexia 32 HP:0001265
30 proximal muscle weakness 32 HP:0003701
31 limb-girdle muscle weakness 59 Frequent (79-30%)
32 peripheral axonal neuropathy 32 HP:0003477
33 distal muscle weakness 32 HP:0002460
34 elevated serum creatine kinase 32 HP:0003236

Symptoms via clinical synopsis from OMIM:

57
Voice:
dysphonia

Abdomen Gastrointestinal:
dysphagia (in some patients)

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

41
Skeletal Muscle, Eye, 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. 8 71
23043144 2012
2
Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension. 71
26874653 2016
3
Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia. 71
21951382 2011
4
RRM2B mutations are frequent in familial PEO with multiple mtDNA deletions. 71
21646632 2011
5
Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain deficiency in childhood. 71
17452231 2007
6
Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion. 71
17073823 2007
7
Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion. 71
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 Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 DGUOK NM_080916.3(DGUOK): c.591G> A (p.Gln197=) single nucleotide variant Pathogenic rs748597500 2:74177859-74177859 2:73950732-73950732
2 DGUOK NM_080916.3(DGUOK): c.603_604GA[1] (p.Arg202fs) short repeat Pathogenic rs863223949 2:74184265-74184266 2:73957138-73957139
3 DGUOK NM_080916.3(DGUOK): c.130G> A (p.Glu44Lys) single nucleotide variant Pathogenic rs762550967 2:74154167-74154167 2:73927040-73927040
4 DGUOK NM_080916.3(DGUOK): c.186C> A (p.Tyr62Ter) single nucleotide variant Pathogenic rs879255617 2:74166080-74166080 2:73938953-73938953
5 DGUOK NM_080916.3(DGUOK): c.444-11C> G single nucleotide variant Pathogenic/Likely pathogenic rs536746349 2:74177701-74177701 2:73950574-73950574
6 DGUOK NM_080916.3(DGUOK): c.137A> G (p.Asn46Ser) single nucleotide variant Pathogenic/Likely pathogenic rs763615602 2:74154174-74154174 2:73927047-73927047
7 DGUOK NM_080916.3(DGUOK): c.462T> A (p.Asn154Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs144181978 2:74177730-74177730 2:73950603-73950603
8 DGUOK NM_080916.3(DGUOK): c.155C> G (p.Ser52Cys) single nucleotide variant Uncertain significance 2:74166049-74166049 2:73938922-73938922
9 DGUOK NM_080916.3(DGUOK): c.509A> G (p.Gln170Arg) single nucleotide variant Benign rs74874677 2:74177777-74177777 2:73950650-73950650

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

74
# 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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