PEOA6
MCID: PRG103
MIFTS: 35

Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 (PEOA6)

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 Dominant 6:

Name: Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 56 29 6
Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant, 6 73 13 71
Peoa6 56 12 73
Autosomal Dominant Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions 6 12 15
Mitochondrial Dna Deletion Syndrome with Limb-Girdle Weakness 12 58
Mitochondrial Dna Deletion Syndrome with Progressive Myopathy 12 58
Mtdna Deletion Syndrome with Limb-Girdle Weakness 12 58
Mtdna Deletion Syndrome with Progressive Myopathy 12 58
Dna2-Related Mitochondrial Dna Deletion Syndrome 12 58
Ophthalmoplegia, External, Progressive, with Mitochondrial Dna Deletions, Autosomal Dominant, Type 6 39
Progressive External Ophthalmoplegia, Autosomal Dominant 6 56
Autosomal Dominant Progressive External Ophthalmoplegia 6 12
Progressive External Ophthalmoplegia Autosomal Dominant 6 73

Characteristics:

Orphanet epidemiological data:

58
dna2-related mitochondrial dna deletion syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
variable age at onset (range childhood to adulthood)


HPO:

31
progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 6:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Progressive External Ophthalmoplegia with Mitochondrial Dna...

OMIM : 56 PEOA6 is characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA (mtDNA) deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression (summary by Ronchi et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640). (615156)

MalaCards based summary : Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6, also known as progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant, 6, is related to rapadilino syndrome and baller-gerold syndrome, and has symptoms including myalgia, muscle cramp and facial paresis. An important gene associated with Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 is DNA2 (DNA Replication Helicase/Nuclease 2), and among its related pathways/superpathways is Cytosolic iron-sulfur cluster assembly. Related phenotypes are progressive external ophthalmoplegia and limb-girdle muscle weakness

Disease Ontology : 12 A chronic progressive external ophthalmoplegia characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance and mtDNA deletions that has material basis in heterozygous mutation in DNA2 on chromosome 10q21.3.

UniProtKB/Swiss-Prot : 73 Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6: A disorder characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression.

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 Dominant 6 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 rapadilino syndrome 9.9 FEN1 DNA2
2 baller-gerold syndrome 9.9 FEN1 DNA2
3 rothmund-thomson syndrome, type 2 9.8 FEN1 DNA2
4 seckel syndrome 8 9.7 RBBP8 DNA2
5 seckel syndrome 2 9.7 RBBP8 DNA2
6 isolated growth hormone deficiency, type ia 9.4 RBBP8 DNA2
7 fanconi anemia, complementation group a 9.1 RBBP8 FEN1 DNA2
8 xeroderma pigmentosum, variant type 8.5 RBBP8 FEN1 DNA2 CIAO2B CIAO1

Graphical network of the top 20 diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6:



Diseases related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6

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

Human phenotypes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive external ophthalmoplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000590
2 limb-girdle muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003325
3 myopathy 58 31 frequent (33%) Frequent (79-30%) HP:0003198
4 hyperlordosis 58 31 frequent (33%) Frequent (79-30%) HP:0003307
5 myalgia 58 31 frequent (33%) Frequent (79-30%) HP:0003326
6 depressivity 58 31 frequent (33%) Frequent (79-30%) HP:0000716
7 multiple joint contractures 58 31 frequent (33%) Frequent (79-30%) HP:0002828
8 slender build 58 31 frequent (33%) Frequent (79-30%) HP:0001533
9 decreased fetal movement 58 31 frequent (33%) Frequent (79-30%) HP:0001558
10 mitochondrial myopathy 58 31 frequent (33%) Frequent (79-30%) HP:0003737
11 obstructive sleep apnea 58 31 occasional (7.5%) Frequent (79-30%) HP:0002870
12 generalized hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001290
13 muscle spasm 58 31 frequent (33%) Frequent (79-30%) HP:0003394
14 exertional dyspnea 58 31 frequent (33%) Frequent (79-30%) HP:0002875
15 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
16 gowers sign 58 31 frequent (33%) Frequent (79-30%) HP:0003391
17 elevated creatine kinase after exercise 58 31 frequent (33%) Frequent (79-30%) HP:0008331
18 decreased facial expression 58 31 frequent (33%) Frequent (79-30%) HP:0004673
19 congenital ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0007970
20 decreased mitochondrial number 58 31 frequent (33%) Frequent (79-30%) HP:0040013
21 gait disturbance 58 31 Frequent (79-30%) HP:0001288
22 elevated serum creatine kinase 31 HP:0003236
23 ptosis 31 HP:0000508
24 facial palsy 31 HP:0010628
25 external ophthalmoplegia 31 HP:0000544
26 generalized amyotrophy 31 HP:0003700
27 exercise intolerance 31 HP:0003546

Symptoms via clinical synopsis from OMIM:

56
Muscle Soft Tissue:
myalgia
gowers sign
exercise intolerance
muscle cramps
abnormal gait
more
Head And Neck Eyes:
external ophthalmoplegia
ptosis, mild

Head And Neck Face:
facial muscle weakness

Growth Other:
slender build

Respiratory:
exertional dyspnea
obstructive sleep apnea (in some patients)

Laboratory Abnormalities:
increased serum creatine kinase

Clinical features from OMIM:

615156

UMLS symptoms related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6:


myalgia, muscle cramp, facial paresis, dyspnea on exertion

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

Search Clinical Trials , NIH Clinical Center for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6

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

Genetic tests related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6:

# Genetic test Affiliating Genes
1 Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 29 DNA2

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

Publications for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Articles related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6:

# Title Authors PMID Year
1
Mutations in DNA2 link progressive myopathy to mitochondrial DNA instability. 56 6
23352259 2013
2
Mitochondrial DNA Maintenance Defects Overview 6
29517884 2018

Variations for Progressive External Ophthalmoplegia with Mitochondrial Dna...

ClinVar genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DNA2 DNA2, ARG284HISSNV Pathogenic 41477
2 DNA2 DNA2, LYS313GLUSNV Pathogenic 41478
3 DNA2 NM_001080449.3(DNA2):c.1909G>A (p.Val637Ile)SNV Pathogenic 41479 10:70191693-70191693 10:68431936-68431936
4 DNA2 NM_001080449.3(DNA2):c.3014C>T (p.Thr1005Ile)SNV Likely pathogenic 522960 rs376624048 10:70176566-70176566 10:68416809-68416809
5 DNA2 NM_001080449.3(DNA2):c.1919C>T (p.Ser640Leu)SNV Likely pathogenic 807407 10:70191683-70191683 10:68431926-68431926

UniProtKB/Swiss-Prot genetic disease variations for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6:

73
# Symbol AA change Variation ID SNP ID
1 DNA2 p.Arg198His VAR_069905 rs127239347
2 DNA2 p.Lys227Glu VAR_069906 rs760412883
3 DNA2 p.Val637Ile VAR_069907 rs746522359

Expression for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Search GEO for disease gene expression data for Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6.

Pathways for Progressive External Ophthalmoplegia with Mitochondrial Dna...

Pathways related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.91 NUBP1 CIAO2B CIAO1

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

Cellular components related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromosome, telomeric region GO:0000784 9.16 FEN1 DNA2
2 MMXD complex GO:0071817 8.96 CIAO2B CIAO1
3 CIA complex GO:0097361 8.8 CIAO2B CIAO2A CIAO1

Biological processes related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.7 RBBP8 FEN1 DNA2
2 DNA repair GO:0006281 9.67 RBBP8 FEN1 DNA2
3 DNA replication GO:0006260 9.61 RBBP8 FEN1 DNA2
4 regulation of signal transduction by p53 class mediator GO:1901796 9.54 RBBP8 DNA2
5 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.54 RBBP8 FEN1 DNA2
6 double-strand break repair via homologous recombination GO:0000724 9.51 RBBP8 FEN1
7 chromosome segregation GO:0007059 9.5 CIAO2B CIAO2A CIAO1
8 base-excision repair GO:0006284 9.48 FEN1 DNA2
9 telomere maintenance via semi-conservative replication GO:0032201 9.46 FEN1 DNA2
10 DNA double-strand break processing GO:0000729 9.4 RBBP8 DNA2
11 protein maturation by [4Fe-4S] cluster transfer GO:0106035 9.26 CIAO2B CIAO2A
12 DNA replication, removal of RNA primer GO:0043137 9.16 FEN1 DNA2
13 protein maturation by iron-sulfur cluster transfer GO:0097428 9.13 CIAO2B CIAO2A CIAO1
14 iron-sulfur cluster assembly GO:0016226 8.92 NUBP1 CIAO2B CIAO2A CIAO1

Molecular functions related to Progressive External Ophthalmoplegia with Mitochondrial Dna Deletions, Autosomal Dominant 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 double-stranded DNA binding GO:0003690 9.4 RBBP8 FEN1
2 iron-sulfur cluster binding GO:0051536 9.37 NUBP1 DNA2
3 nuclease activity GO:0004518 9.33 RBBP8 FEN1 DNA2
4 damaged DNA binding GO:0003684 9.32 RBBP8 FEN1
5 4 iron, 4 sulfur cluster binding GO:0051539 9.26 NUBP1 DNA2
6 5'-flap endonuclease activity GO:0017108 8.96 FEN1 DNA2
7 endonuclease activity GO:0004519 8.8 RBBP8 FEN1 DNA2

Sources for Progressive External Ophthalmoplegia with Mitochondrial Dna...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....