MTDPS11
MCID: MTC078
MIFTS: 37

Mitochondrial Dna Depletion Syndrome 11 (MTDPS11)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 11

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 11:

Name: Mitochondrial Dna Depletion Syndrome 11 56 12 73 29 13 6 15 71
Progressive External Ophthalmoplegia-Myopathy-Emaciation Syndrome 12 58
Mtdps11 56 73
Mitochondrial Dna Maintenance Syndrome Due to Mgme1 Deficiency 58
Mtdna Maintenance Syndrome Due to Mgme1 Deficiency 58
Mitochondrial Dna Depletion Syndrome, Type 11 39
Peo-Myopathy-Emaciation Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
progressive external ophthalmoplegia-myopathy-emaciation syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
variable age at onset (range first to fourth decade)


HPO:

31
mitochondrial dna depletion syndrome 11:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


Summaries for Mitochondrial Dna Depletion Syndrome 11

OMIM : 56 Mitochondrial DNA depletion syndrome-11 is an autosomal recessive mitochondrial disorder characterized by onset in childhood or adulthood of progressive external ophthalmoplegia (PEO), muscle weakness and atrophy, exercise intolerance, and respiratory insufficiency due to muscle weakness. More variable features include spinal deformity, emaciation, and cardiac abnormalities. Skeletal muscle biopsies show deletion and depletion of mitochondrial DNA (mtDNA) with variable defects in respiratory chain enzyme activities (summary by Kornblum et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (615084)

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 11, also known as progressive external ophthalmoplegia-myopathy-emaciation syndrome, is related to mitochondrial dna depletion syndrome 2 and mitochondrial dna depletion syndrome 4a, and has symptoms including dyspnea and facial paresis. An important gene associated with Mitochondrial Dna Depletion Syndrome 11 is MGME1 (Mitochondrial Genome Maintenance Exonuclease 1), and among its related pathways/superpathways is Mitochondrial Gene Expression. Affiliated tissues include skeletal muscle and eye, and related phenotypes are progressive external ophthalmoplegia and kyphosis

Disease Ontology : 12 A mitochondrial DNA depletion syndrome that is characterized by onset in childhood or adulthood of progressive external ophthalmoplegia (PEO), muscle weakness and atrophy, exercise intolerance, and respiratory insufficiency due to muscle weakness, and has material basis in autosomal recessive inheritance of homozygous mutation in the mitochondrial genome maintenance exonuclease 1 gene on chromosome 20p11.

UniProtKB/Swiss-Prot : 73 Mitochondrial DNA depletion syndrome 11: An autosomal recessive mitochondrial disorder characterized by onset in childhood or adulthood of progressive external ophthalmoplegia, muscle weakness and atrophy, exercise intolerance, and respiratory insufficiency due to muscle weakness. More variable features include spinal deformity, emaciation, and cardiac abnormalities. Skeletal muscle biopsies show deletion and depletion of mitochondrial DNA (mtDNA) with variable defects in respiratory chain enzyme activities.

Related Diseases for Mitochondrial Dna Depletion Syndrome 11

Diseases in the Mitochondrial Dna Depletion Syndrome family:

Mitochondrial Dna Depletion Syndrome 4a Mitochondrial Dna Depletion Syndrome 9
Mitochondrial Dna Depletion Syndrome 3 Mitochondrial Dna Depletion Syndrome 6
Mitochondrial Dna Depletion Syndrome 7 Mitochondrial Dna Depletion Syndrome 1
Mitochondrial Dna Depletion Syndrome 2 Mitochondrial Dna Depletion Syndrome 5
Mitochondrial Dna Depletion Syndrome 8a Mitochondrial Dna Depletion Syndrome 4b
Mitochondrial Dna Depletion Syndrome 11 Mitochondrial Dna Depletion Syndrome 12b , Autosomal Recessive
Mitochondrial Dna Depletion Syndrome 13 Mitochondrial Dna Depletion Syndrome 14
Mitochondrial Dna Depletion Syndrome 15 Mitochondrial Dna Depletion Syndrome 12a , Autosomal Dominant
Mitochondrial Dna Depletion Syndrome 16 Mitochondrial Dna Depletion Syndrome 17
Mitochondrial Dna Depletion Syndrome 18 Mitochondrial Dna Depletion Syndrome 12a
Mitochondrial Dna Depletion Syndrome 12b Mitochondrial Dna Deletion Syndromes
Multiple Mitochondrial Dna Deletion Syndrome

Diseases related to Mitochondrial Dna Depletion Syndrome 11 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 mitochondrial dna depletion syndrome 2 9.9 TEFM PRIMPOL
2 mitochondrial dna depletion syndrome 4a 9.9 PRIMPOL MGME1
3 refractive error 9.7 RDH5 PRIMPOL
4 deafness, aminoglycoside-induced 9.5 TFB2M TFB1M
5 leber optic atrophy 9.2 TFB2M TFB1M
6 mitochondrial metabolism disease 9.1 TFB2M TFB1M MGME1
7 charcot-marie-tooth disease type 2a2b 8.9 UQCC2 TFB1M TEFM PRIMPOL MGME1
8 mitochondrial dna depletion syndrome 14 8.8 UQCC2 TFB1M TEFM PRIMPOL MGME1
9 mitochondrial dna depletion syndrome 8a 8.8 UQCC2 TFB1M TEFM PRIMPOL MGME1
10 mitochondrial dna depletion syndrome 1 8.2 UQCC2 TFB2M TFB1M TEFM PRIMPOL MGME1

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 11:



Diseases related to Mitochondrial Dna Depletion Syndrome 11

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 11

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 11:

58 31 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 progressive external ophthalmoplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000590
2 kyphosis 58 31 frequent (33%) Frequent (79-30%) HP:0002808
3 myopathy 58 31 frequent (33%) Frequent (79-30%) HP:0003198
4 dysphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002015
5 dyspnea 58 31 frequent (33%) Frequent (79-30%) HP:0002094
6 elevated serum creatine kinase 58 31 frequent (33%) Frequent (79-30%) HP:0003236
7 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
8 dilated cardiomyopathy 58 31 occasional (7.5%) Frequent (79-30%) HP:0001644
9 spinal rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0003306
10 ragged-red muscle fibers 58 31 frequent (33%) Frequent (79-30%) HP:0003200
11 easy fatigability 58 31 frequent (33%) Frequent (79-30%) HP:0003388
12 nasal speech 58 31 frequent (33%) Frequent (79-30%) HP:0001611
13 dysphonia 58 31 frequent (33%) Frequent (79-30%) HP:0001618
14 hyporeflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001265
15 respiratory failure 58 31 frequent (33%) Frequent (79-30%) HP:0002878
16 recurrent infections 58 31 frequent (33%) Frequent (79-30%) HP:0002719
17 generalized amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003700
18 exercise intolerance 58 31 frequent (33%) Frequent (79-30%) HP:0003546
19 nausea 58 31 occasional (7.5%) Frequent (79-30%) HP:0002018
20 spinal deformities 58 31 frequent (33%) Frequent (79-30%) HP:0008443
21 weakness of facial musculature 58 31 frequent (33%) Frequent (79-30%) HP:0030319
22 decreased mitochondrial number 58 31 frequent (33%) Frequent (79-30%) HP:0040013
23 intellectual disability 58 31 occasional (7.5%) Very rare (<4-1%) HP:0001249
24 microcephaly 58 31 occasional (7.5%) Very rare (<4-1%) HP:0000252
25 respiratory insufficiency due to muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0002747
26 arrhythmia 58 31 occasional (7.5%) Very rare (<4-1%) HP:0011675
27 nephrolithiasis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000787
28 diarrhea 58 31 occasional (7.5%) Very rare (<4-1%) HP:0002014
29 poor appetite 58 31 occasional (7.5%) Occasional (29-5%) HP:0004396
30 cerebellar hypoplasia 31 occasional (7.5%) HP:0001321
31 cerebellar atrophy 58 31 very rare (1%) Very rare (<4-1%) HP:0001272
32 hypergonadotropic hypogonadism 58 31 very rare (1%) Very rare (<4-1%) HP:0000815
33 respiratory insufficiency 31 HP:0002093
34 facial palsy 31 HP:0010628
35 proximal amyotrophy 31 HP:0007126
36 diplopia 58 Excluded (0%)

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
kyphosis
spinal deformities
rigid spine

Head And Neck Eyes:
ptosis
progressive external ophthalmoplegia

Voice:
nasal speech
dysphonia

Head And Neck Face:
facial weakness

Head And Neck Head:
microcephaly (in 1 family)

Laboratory Abnormalities:
increased serum creatine kinase, mild

Cardiovascular Heart:
cardiomyopathy, dilated (in 1 patient)
arrhythmias (in 1 patient)

Endocrine Features:
hypergonadotropic hypogonadism (reported in 1 female)

Respiratory:
dyspnea
recurrent infections
respiratory insufficiency, severe, due to muscle weakness
ventilation may be required

Muscle Soft Tissue:
easy fatigability
exercise intolerance
muscle atrophy, proximal
cox-negative fibers
muscle atrophy, generalized
more
Neurologic Peripheral Nervous System:
hyporeflexia

Neurologic Central Nervous System:
mental retardation (reported in 1 family)
cerebellar hypoplasia (reported in 1 family)

Abdomen Gastrointestinal:
diarrhea (in some patients)
gastrointestinal symptoms (in some patients)
nausea (in some patients)
abdominal fullness (in some patients)
loss of appetite (in some patients)

Growth Weight:
emaciation, profound

Genitourinary Kidneys:
renal colic (in some patients)

Clinical features from OMIM:

615084

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 11:


dyspnea, facial paresis

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 11

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 11

Genetic Tests for Mitochondrial Dna Depletion Syndrome 11

Genetic tests related to Mitochondrial Dna Depletion Syndrome 11:

# Genetic test Affiliating Genes
1 Mitochondrial Dna Depletion Syndrome 11 29 MGME1

Anatomical Context for Mitochondrial Dna Depletion Syndrome 11

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 11:

40
Skeletal Muscle, Eye

Publications for Mitochondrial Dna Depletion Syndrome 11

Articles related to Mitochondrial Dna Depletion Syndrome 11:

# Title Authors PMID Year
1
Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. 6 56
23313956 2013
2
Mitochondrial DNA Maintenance Defects Overview 6
29517884 2018

Variations for Mitochondrial Dna Depletion Syndrome 11

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 11:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MGME1 NM_052865.4(MGME1):c.359del (p.Pro120fs)deletion Pathogenic 428588 rs1555789140 20:17950860-17950860 20:17970217-17970217
2 MGME1 NM_052865.4(MGME1):c.456G>A (p.Trp152Ter)SNV Pathogenic 40051 rs587776943 20:17950958-17950958 20:17970315-17970315
3 MGME1 NM_052865.4(MGME1):c.698A>G (p.Tyr233Cys)SNV Pathogenic 40052 rs587776944 20:17956513-17956513 20:17975870-17975870
4 MGME1 NM_052865.4(MGME1):c.794C>T (p.Thr265Ile)SNV Conflicting interpretations of pathogenicity 235425 rs76599088 20:17968871-17968871 20:17988228-17988228
5 MGME1 NM_052865.4(MGME1):c.532C>T (p.Arg178Trp)SNV Conflicting interpretations of pathogenicity 445604 rs143417446 20:17956347-17956347 20:17975704-17975704

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 11:

73
# Symbol AA change Variation ID SNP ID
1 MGME1 p.Tyr233Cys VAR_069102 rs587776944

Expression for Mitochondrial Dna Depletion Syndrome 11

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 11.

Pathways for Mitochondrial Dna Depletion Syndrome 11

Pathways related to Mitochondrial Dna Depletion Syndrome 11 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.76 TFB2M TFB1M

GO Terms for Mitochondrial Dna Depletion Syndrome 11

Cellular components related to Mitochondrial Dna Depletion Syndrome 11 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.63 UQCC2 TFB2M TFB1M TEFM PRIMPOL MGME1
2 mitochondrial matrix GO:0005759 9.35 UQCC2 TFB2M TFB1M TEFM PRIMPOL
3 mitochondrial nucleoid GO:0042645 8.92 UQCC2 TFB2M TFB1M TEFM

Biological processes related to Mitochondrial Dna Depletion Syndrome 11 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 rRNA processing GO:0006364 9.4 TFB2M TFB1M
2 mitochondrion organization GO:0007005 9.37 TFB2M TFB1M
3 rRNA methylation GO:0031167 9.32 TFB2M TFB1M
4 mitochondrial transcription GO:0006390 9.26 TFB2M TEFM
5 rRNA modification GO:0000154 9.16 TFB2M TFB1M
6 mitochondrial DNA repair GO:0043504 8.96 PRIMPOL MGME1
7 mitochondrial DNA replication GO:0006264 8.8 TEFM PRIMPOL MGME1

Molecular functions related to Mitochondrial Dna Depletion Syndrome 11 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 rRNA methyltransferase activity GO:0008649 8.96 TFB2M TFB1M
2 rRNA (adenine-N6,N6-)-dimethyltransferase activity GO:0000179 8.62 TFB2M TFB1M

Sources for Mitochondrial Dna Depletion Syndrome 11

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
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