CNM1
MCID: MYP123
MIFTS: 43

Myopathy, Centronuclear, 1 (CNM1)

Categories: Bone diseases, Cardiovascular diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Myopathy, Centronuclear, 1

MalaCards integrated aliases for Myopathy, Centronuclear, 1:

Name: Myopathy, Centronuclear, 1 58 54 76 30 6
Myopathy, Centronuclear, Autosomal Dominant 58 74
Autosomal Dominant Centronuclear Myopathy 54 60
Myotubular Myopathy, Autosomal Dominant 58 54
Autosomal Dominant Myotubular Myopathy 76 74
Ad-Cnm 54 60
Cnm1 58 76
Centronuclear Myopathy, Autosomal, Modifier of 58
Centronuclear Myopathy Autosomal Dominant 76
Dnm2-Related Centronuclear Myopathy 54
Myopathy, Centronuclear, Type 1 41
Centronuclear Myopathy 1 58

Characteristics:

Orphanet epidemiological data:

60
autosomal dominant centronuclear myopathy
Inheritance: Autosomal dominant; Age of onset: Adolescent,Childhood,Infancy;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
variable age of onset (range early childhood to adult)


HPO:

33
myopathy, centronuclear, 1:
Onset and clinical course slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Myopathy, Centronuclear, 1

NIH Rare Diseases : 54 Autosomal dominant centronuclear myopathy (AD-CNM) is a type of centronuclear myopathy, which is a group of rare, inherited conditions that affect the muscles. In AD-CNM, specifically, the severity of the condition and the associated signs and symptoms vary significantly among affected people. In people with a mild form, features of the condition generally don't develop until adolescence or early adulthood and may include slowly progressive muscle weakness, muscle pain with exercise and difficulty walking. Although some affected people will eventually lose the ability to walk, this usually does not occur before the 6th decade of life. In more severe cases, affected people may develop symptoms during infancy or early childhood such as hypotonia and generalized weakness. These children generally have delayed motor milestones and often need wheelchair assistance in childhood or adolescence. Most cases of AD-CNM are caused by changes (mutations) in the DNM2 gene; however, some affected families are reported to have mutations in the MYF6 or CCDC78 genes. The condition is inherited in an autosomal dominant manner. Treatment is based on the signs and symptoms present in each person and may include physical and/or occupational therapy and assistive devices to help with mobility, eating and/or breathing.

MalaCards based summary : Myopathy, Centronuclear, 1, also known as myopathy, centronuclear, autosomal dominant, is related to centronuclear myopathy and myopathy, centronuclear, 5, and has symptoms including ophthalmoparesis and facial paresis. An important gene associated with Myopathy, Centronuclear, 1 is DNM2 (Dynamin 2), and among its related pathways/superpathways are Ca, cAMP and Lipid Signaling and Fc gamma R-mediated phagocytosis. Affiliated tissues include eye, skeletal muscle and bone, and related phenotypes are centrally nucleated skeletal muscle fibers and ptosis

OMIM : 58 Autosomal dominant centronuclear myopathy is a congenital myopathy characterized by slowly progressive muscular weakness and wasting. The disorder involves mainly limb girdle, trunk, and neck muscles but may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life, and some affected individuals become wheelchair-bound in their fifties. Ptosis and limitation of eye movements occur frequently. The most prominent histopathologic features include high frequency of centrally located nuclei in a large number of extrafusal muscle fibers (which is the basis of the name of the disorder), radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers (summary by Bitoun et al., 2005). (160150)

UniProtKB/Swiss-Prot : 76 Myopathy, centronuclear, 1: A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.

Related Diseases for Myopathy, Centronuclear, 1

Diseases in the Centronuclear Myopathy family:

Myopathy, Centronuclear, 1 Myopathy, Centronuclear, 2
Myopathy, Centronuclear, 4 Myopathy, Centronuclear, 5

Diseases related to Myopathy, Centronuclear, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 centronuclear myopathy 30.2 BIN1 DNM2 MTMR14 MYF6 RYR1
2 myopathy, centronuclear, 5 11.1
3 myopathy, centronuclear, 6, with fiber-type disproportion 11.1
4 myopathy 10.5
5 muscle disorders 10.4
6 myotonia 10.4
7 charcot-marie-tooth disease, dominant intermediate b 9.9 DNM2 RYR1
8 myopathy, centronuclear, 2 9.9 BIN1 RYR1
9 myopathy, congenital 9.8 DNM2 RYR1
10 ptosis 9.7 DNM2 RYR1
11 muscular disease 9.4 DNM2 MYF6 RYR1

Graphical network of the top 20 diseases related to Myopathy, Centronuclear, 1:



Diseases related to Myopathy, Centronuclear, 1

Symptoms & Phenotypes for Myopathy, Centronuclear, 1

Human phenotypes related to Myopathy, Centronuclear, 1:

60 33 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 centrally nucleated skeletal muscle fibers 60 33 hallmark (90%) Very frequent (99-80%) HP:0003687
2 ptosis 60 33 frequent (33%) Frequent (79-30%) HP:0000508
3 emg: myopathic abnormalities 60 33 frequent (33%) Frequent (79-30%) HP:0003458
4 proximal muscle weakness in lower limbs 60 33 frequent (33%) Frequent (79-30%) HP:0008994
5 proximal muscle weakness in upper limbs 60 33 frequent (33%) Frequent (79-30%) HP:0008997
6 type 1 muscle fiber predominance 60 33 frequent (33%) Frequent (79-30%) HP:0003803
7 thin ribs 60 33 frequent (33%) Frequent (79-30%) HP:0000883
8 polyhydramnios 60 33 frequent (33%) Frequent (79-30%) HP:0001561
9 difficulty walking 60 33 frequent (33%) Frequent (79-30%) HP:0002355
10 decreased fetal movement 60 33 frequent (33%) Frequent (79-30%) HP:0001558
11 large for gestational age 60 33 frequent (33%) Frequent (79-30%) HP:0001520
12 generalized hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0001290
13 muscle fibrillation 60 33 frequent (33%) Frequent (79-30%) HP:0010546
14 abnormality of the foot musculature 60 33 frequent (33%) Frequent (79-30%) HP:0001436
15 delayed gross motor development 60 33 frequent (33%) Frequent (79-30%) HP:0002194
16 macrocephaly at birth 60 33 frequent (33%) Frequent (79-30%) HP:0004488
17 spontaneous abortion 60 33 frequent (33%) Frequent (79-30%) HP:0005268
18 mildly elevated creatine kinase 33 frequent (33%) HP:0008180
19 respiratory insufficiency due to muscle weakness 60 33 occasional (7.5%) Occasional (29-5%) HP:0002747
20 cavernous hemangioma 60 33 occasional (7.5%) Occasional (29-5%) HP:0001048
21 cryptorchidism 60 33 occasional (7.5%) Occasional (29-5%) HP:0000028
22 areflexia of lower limbs 60 33 occasional (7.5%) Occasional (29-5%) HP:0002522
23 pyloric stenosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002021
24 urinary incontinence 60 33 occasional (7.5%) Occasional (29-5%) HP:0000020
25 external ophthalmoplegia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000544
26 peripheral axonal neuropathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0003477
27 exercise-induced myalgia 60 33 occasional (7.5%) Occasional (29-5%) HP:0003738
28 calf muscle hypertrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0008981
29 neonatal asphyxia 60 33 occasional (7.5%) Occasional (29-5%) HP:0012768
30 skeletal muscle hypertrophy 33 occasional (7.5%) HP:0003712
31 malignant hyperthermia 60 33 very rare (1%) Very rare (<4-1%) HP:0002047
32 hyperlordosis 33 HP:0003307
33 facial palsy 33 HP:0010628
34 flexion contracture 33 HP:0001371
35 motor delay 33 HP:0001270
36 easy fatigability 33 HP:0003388
37 areflexia 33 HP:0001284
38 proximal muscle weakness 33 HP:0003701
39 mildly elevated creatine phosphokinase 60 Frequent (79-30%)
40 sleepy facial expression 33 HP:0005335

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
ptosis
ophthalmoparesis

Muscle Soft Tissue:
delayed motor development
muscle weakness, primarily proximal
distal muscle weakness may occur
muscle hypertrophy may occur
muscle biopsy shows centralized nuclei
more
Skeletal:
contractures

Neurologic Peripheral Nervous System:
areflexia

Head And Neck Face:
facial muscle weakness

Neurologic Central Nervous System:
walking difficulties

Clinical features from OMIM:

160150

UMLS symptoms related to Myopathy, Centronuclear, 1:


ophthalmoparesis, facial paresis

GenomeRNAi Phenotypes related to Myopathy, Centronuclear, 1 according to GeneCards Suite gene sharing:

27 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 9.44 MYF6
2 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.44 DNM2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.44 DNM2 MYF6
4 Increased shRNA abundance (Z-score > 2) GR00366-A-122 9.44 DNM2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-124 9.44 MYF6
6 Increased shRNA abundance (Z-score > 2) GR00366-A-13 9.44 DNM2 MYF6
7 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.44 MYF6
8 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.44 MYF6
9 Increased shRNA abundance (Z-score > 2) GR00366-A-189 9.44 MYF6
10 Increased shRNA abundance (Z-score > 2) GR00366-A-198 9.44 MYF6
11 Increased shRNA abundance (Z-score > 2) GR00366-A-30 9.44 DNM2

MGI Mouse Phenotypes related to Myopathy, Centronuclear, 1:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.46 BIN1 DNM2 MTMR14 RYR1
2 homeostasis/metabolism MP:0005376 9.35 BIN1 DNM2 MTMR14 MYF6 RYR1
3 muscle MP:0005369 9.02 BIN1 DNM2 MTMR14 MYF6 RYR1

Drugs & Therapeutics for Myopathy, Centronuclear, 1

Search Clinical Trials , NIH Clinical Center for Myopathy, Centronuclear, 1

Genetic Tests for Myopathy, Centronuclear, 1

Genetic tests related to Myopathy, Centronuclear, 1:

# Genetic test Affiliating Genes
1 Myopathy, Centronuclear, 1 30 DNM2 MTMR14

Anatomical Context for Myopathy, Centronuclear, 1

MalaCards organs/tissues related to Myopathy, Centronuclear, 1:

42
Eye, Skeletal Muscle, Bone

Publications for Myopathy, Centronuclear, 1

Articles related to Myopathy, Centronuclear, 1:

# Title Authors Year
1
Adult-onset autosomal dominant centronuclear myopathy due to BIN1 mutations. ( 25260562 )
2014
2
Clinical utility gene card for: Centronuclear and myotubular myopathies. ( 22617344 )
2012
3
Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy. ( 22396310 )
2012
4
Autosomal dominant centronuclear myopathy with unique clinical presentations. ( 18162732 )
2007
5
A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy. ( 17008356 )
2006
6
Mutations in dynamin 2 cause dominant centronuclear myopathy. ( 16227997 )
2005
7
Autosomal dominant centronuclear myopathy: report of a new family with clinical features simulating facioscapulohumeral syndrome. ( 9270681 )
1997

Variations for Myopathy, Centronuclear, 1

UniProtKB/Swiss-Prot genetic disease variations for Myopathy, Centronuclear, 1:

76 (show all 19)
# Symbol AA change Variation ID SNP ID
1 DNM2 p.Glu368Lys VAR_031962 rs121909092
2 DNM2 p.Arg369Gln VAR_031963 rs121909089
3 DNM2 p.Arg369Trp VAR_031964 rs121909090
4 DNM2 p.Arg465Trp VAR_031965 rs121909091
5 DNM2 p.Ala618Thr VAR_039041
6 DNM2 p.Ser619Leu VAR_039042 rs121909095
7 DNM2 p.Ser619Trp VAR_039043 rs121909095
8 DNM2 p.Glu650Lys VAR_062576
9 DNM2 p.Glu368Gln VAR_068365
10 DNM2 p.Arg522Cys VAR_068366
11 DNM2 p.Arg522His VAR_068367 rs587783595
12 DNM2 p.Arg523Gly VAR_068368 rs587783596
13 DNM2 p.Glu560Lys VAR_068369 rs879254086
14 DNM2 p.Ala618Asp VAR_068370
15 DNM2 p.Leu621Pro VAR_068371 rs587783597
16 DNM2 p.Pro627His VAR_068372
17 DNM2 p.Pro627Arg VAR_068373 rs587783598
18 MTMR14 p.Arg336Gln VAR_033370 rs121434509
19 MTMR14 p.Tyr462Cys VAR_033371 rs121434510

ClinVar genetic disease variations for Myopathy, Centronuclear, 1:

6 (show all 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 DNM2 NM_001005360.2(DNM2): c.1106G> A (p.Arg369Gln) single nucleotide variant Pathogenic rs121909089 GRCh37 Chromosome 19, 10904509: 10904509
2 DNM2 NM_001005360.2(DNM2): c.1106G> A (p.Arg369Gln) single nucleotide variant Pathogenic rs121909089 GRCh38 Chromosome 19, 10793833: 10793833
3 DNM2 NM_001005360.2(DNM2): c.1105C> T (p.Arg369Trp) single nucleotide variant Pathogenic rs121909090 GRCh37 Chromosome 19, 10904508: 10904508
4 DNM2 NM_001005360.2(DNM2): c.1105C> T (p.Arg369Trp) single nucleotide variant Pathogenic rs121909090 GRCh38 Chromosome 19, 10793832: 10793832
5 DNM2 NM_001005360.2(DNM2): c.1393C> T (p.Arg465Trp) single nucleotide variant Pathogenic rs121909091 GRCh37 Chromosome 19, 10909219: 10909219
6 DNM2 NM_001005360.2(DNM2): c.1393C> T (p.Arg465Trp) single nucleotide variant Pathogenic rs121909091 GRCh38 Chromosome 19, 10798543: 10798543
7 DNM2 NM_001005360.2(DNM2): c.1102G> A (p.Glu368Lys) single nucleotide variant Pathogenic rs121909092 GRCh37 Chromosome 19, 10904505: 10904505
8 DNM2 NM_001005360.2(DNM2): c.1102G> A (p.Glu368Lys) single nucleotide variant Pathogenic rs121909092 GRCh38 Chromosome 19, 10793829: 10793829
9 DNM2 NM_001005360.2(DNM2): c.1856C> T (p.Ser619Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121909095 GRCh37 Chromosome 19, 10934538: 10934538
10 DNM2 NM_001005360.2(DNM2): c.1856C> T (p.Ser619Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121909095 GRCh38 Chromosome 19, 10823862: 10823862
11 DNM2 NM_001005360.2(DNM2): c.1565G> A (p.Arg522His) single nucleotide variant Pathogenic rs587783595 GRCh37 Chromosome 19, 10922947: 10922947
12 DNM2 NM_001005360.2(DNM2): c.1565G> A (p.Arg522His) single nucleotide variant Pathogenic rs587783595 GRCh38 Chromosome 19, 10812271: 10812271
13 DNM2 NM_001005360.2(DNM2): c.2179C> T (p.His727Tyr) single nucleotide variant Uncertain significance rs142963320 GRCh37 Chromosome 19, 10939832: 10939832
14 DNM2 NM_001005360.2(DNM2): c.2179C> T (p.His727Tyr) single nucleotide variant Uncertain significance rs142963320 GRCh38 Chromosome 19, 10829156: 10829156
15 DNM2 NM_001005360.2(DNM2): c.1090C> T (p.Arg364Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 10904493: 10904493
16 DNM2 NM_001005360.2(DNM2): c.1090C> T (p.Arg364Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 10793817: 10793817
17 DNM2 NM_001005360.2(DNM2): c.197G> A (p.Arg66Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 10870449: 10870449
18 DNM2 NM_001005360.2(DNM2): c.197G> A (p.Arg66Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 10759773: 10759773
19 MTMR14 NM_001077525.2(MTMR14): c.1790G> A (p.Arg597Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 3, 9701810: 9701810
20 MTMR14 NM_001077525.2(MTMR14): c.1790G> A (p.Arg597Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 3, 9743494: 9743494

Expression for Myopathy, Centronuclear, 1

Search GEO for disease gene expression data for Myopathy, Centronuclear, 1.

Pathways for Myopathy, Centronuclear, 1

Pathways related to Myopathy, Centronuclear, 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.26 MTMR14 RYR1
2 10.91 BIN1 DNM2
3 10.27 BIN1 DNM2

GO Terms for Myopathy, Centronuclear, 1

Cellular components related to Myopathy, Centronuclear, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Z disc GO:0030018 9.16 BIN1 RYR1
2 T-tubule GO:0030315 8.96 BIN1 RYR1
3 I band GO:0031674 8.62 BIN1 RYR1

Biological processes related to Myopathy, Centronuclear, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endocytosis GO:0006897 8.96 BIN1 DNM2
2 membrane organization GO:0061024 8.62 BIN1 DNM2

Molecular functions related to Myopathy, Centronuclear, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protease binding GO:0002020 8.62 BIN1 RYR1

Sources for Myopathy, Centronuclear, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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