CNM1
MCID: MYP123
MIFTS: 47

Myopathy, Centronuclear, 1 (CNM1)

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

Aliases & Classifications for Myopathy, Centronuclear, 1

MalaCards integrated aliases for Myopathy, Centronuclear, 1:

Name: Myopathy, Centronuclear, 1 56 52 73 29 6
Autosomal Dominant Centronuclear Myopathy 12 52 58
Ad-Cnm 12 52 58
Cnm1 56 12 73
Centronuclear Myopathy, Autosomal, Modifier of 56 29
Myopathy, Centronuclear, Autosomal Dominant 56 71
Myotubular Myopathy, Autosomal Dominant 56 52
Autosomal Dominant Myotubular Myopathy 73 71
Centronuclear Myopathy 1 56 12
Centronuclear Myopathy Autosomal Dominant 73
Dnm2-Related Centronuclear Myopathy 52
Myopathy, Centronuclear, Type 1 39

Characteristics:

Orphanet epidemiological data:

58
autosomal dominant centronuclear myopathy
Inheritance: Autosomal dominant; Age of onset: Adolescent,Childhood,Infancy;

OMIM:

56
Inheritance:
autosomal dominant

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


HPO:

31
myopathy, centronuclear, 1:
Inheritance autosomal dominant inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Myopathy, Centronuclear, 1

NIH Rare Diseases : 52 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 autosomal dominant centronuclear myopathy, is related to myopathy, centronuclear, 2 and centronuclear myopathy, 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 Fc gamma R-mediated phagocytosis and C-MYB transcription factor network. Affiliated tissues include eye, skeletal muscle and bone, and related phenotypes are centrally nucleated skeletal muscle fibers and ptosis

Disease Ontology : 12 An autosomal dominant centronuclear myopathy characterized by slowly progressive muscle wasting and weakness involving mainly the limb girdle, trunk, and neck muscles that has material basis in heterozygous mutation in DNM2 on 19p13.2.

OMIM : 56 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 : 73 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 42)
# Related Disease Score Top Affiliating Genes
1 myopathy, centronuclear, 2 29.8 RYR1 BIN1
2 centronuclear myopathy 29.7 RYR1 MYF6 MTMR14 MTM1 DNM2 BIN1
3 peripheral nervous system disease 29.6 RYR1 MTM1 DNM2
4 ptosis 28.6 RYR1 MTMR14 MTM1 DNM2 BIN1
5 myopathy 28.3 RYR1 MYF6 MTMR14 MTM1 DNM2 BIN1
6 myopathy, centronuclear, 4 11.4
7 myopathy, centronuclear, 5 11.3
8 myopathy, centronuclear, 6, with fiber-type disproportion 11.3
9 central core disease of muscle 10.4
10 kearns-sayre syndrome 10.4
11 muscular dystrophy, congenital, lmna-related 10.4
12 muscular dystrophy 10.4
13 myotonia 10.4
14 strabismus 10.2
15 miyoshi muscular dystrophy 10.2
16 neuropathy 10.2
17 mechanical strabismus 10.2
18 myopathy, centronuclear, x-linked 10.0 MTM1 DNM2
19 charcot-marie-tooth disease intermediate type 10.0 MTM1 DNM2
20 retinitis pigmentosa 58 10.0 MYOD1 MYF6
21 charcot-marie-tooth disease, type 4b2 10.0 MTM1 DNM2
22 charcot-marie-tooth disease, type 4b1 9.9 MTM1 DNM2
23 pleomorphic rhabdomyosarcoma 9.9 MYOD1 MYF6
24 arthrogryposis, distal, type 1a 9.9 RYR1 MYOD1
25 hemophagocytic lymphohistiocytosis, familial, 1 9.8 MYOD1 MYF6
26 fetal akinesia deformation sequence 1 9.8 RYR1 MYOD1
27 skeletal muscle cancer 9.8 MYOD1 MYF6
28 congenital structural myopathy 9.8 RYR1 MTM1
29 myopathy, tubular aggregate, 1 9.8 RYR1 MTM1
30 muscle cancer 9.7 MYOD1 MYF6
31 charcot-marie-tooth disease, dominant intermediate b 9.7 MTMR14 MTM1 DNM2
32 alveolar soft part sarcoma 9.7 MYOD1 MYF6
33 central core myopathy 9.6 RYR1 MTM1 DNM2
34 ocular motility disease 9.6 RYR1 MTM1 DNM2
35 myopathy, congenital 9.6 RYR1 MTM1 DNM2
36 rhabdomyosarcoma 2 9.5 MYOD1 MYF6
37 congenital myasthenic syndrome 9.5 RYR1 MTM1 DNM2
38 muscle tissue disease 9.5 RYR1 MYOD1 MTM1
39 distal arthrogryposis 9.5 RYR1 MYOD1 MTM1
40 neuromuscular disease 9.2 RYR1 MYOD1 MTM1 DNM2
41 congenital fiber-type disproportion 8.3 RYR1 MYF6 MTMR14 MTM1 DNM2 BIN1
42 muscular disease 7.9 RYR1 MYOD1 MYF6 MTMR14 MTM1 DNM2

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:

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 centrally nucleated skeletal muscle fibers 58 31 hallmark (90%) Very frequent (99-80%) HP:0003687
2 ptosis 58 31 frequent (33%) Frequent (79-30%) HP:0000508
3 delayed gross motor development 58 31 frequent (33%) Frequent (79-30%) HP:0002194
4 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
5 generalized hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001290
6 emg: myopathic abnormalities 58 31 frequent (33%) Frequent (79-30%) HP:0003458
7 proximal muscle weakness in lower limbs 58 31 frequent (33%) Frequent (79-30%) HP:0008994
8 proximal muscle weakness in upper limbs 58 31 frequent (33%) Frequent (79-30%) HP:0008997
9 type 1 muscle fiber predominance 58 31 frequent (33%) Frequent (79-30%) HP:0003803
10 thin ribs 58 31 frequent (33%) Frequent (79-30%) HP:0000883
11 decreased fetal movement 58 31 frequent (33%) Frequent (79-30%) HP:0001558
12 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
13 large for gestational age 58 31 frequent (33%) Frequent (79-30%) HP:0001520
14 muscle fibrillation 58 31 frequent (33%) Frequent (79-30%) HP:0010546
15 abnormality of the foot musculature 58 31 frequent (33%) Frequent (79-30%) HP:0001436
16 macrocephaly at birth 58 31 frequent (33%) Frequent (79-30%) HP:0004488
17 spontaneous abortion 58 31 frequent (33%) Frequent (79-30%) HP:0005268
18 mildly elevated creatine kinase 31 frequent (33%) HP:0008180
19 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
20 respiratory insufficiency due to muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0002747
21 cavernous hemangioma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001048
22 areflexia of lower limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0002522
23 pyloric stenosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002021
24 external ophthalmoplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000544
25 urinary incontinence 58 31 occasional (7.5%) Occasional (29-5%) HP:0000020
26 peripheral axonal neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003477
27 exercise-induced myalgia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003738
28 calf muscle hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008981
29 neonatal asphyxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012768
30 skeletal muscle hypertrophy 31 occasional (7.5%) HP:0003712
31 malignant hyperthermia 58 31 very rare (1%) Very rare (<4-1%) HP:0002047
32 facial palsy 31 HP:0010628
33 hyperlordosis 31 HP:0003307
34 flexion contracture 31 HP:0001371
35 areflexia 31 HP:0001284
36 motor delay 31 HP:0001270
37 easy fatigability 31 HP:0003388
38 proximal muscle weakness 31 HP:0003701
39 mildly elevated creatine phosphokinase 58 Frequent (79-30%)
40 sleepy facial expression 31 HP:0005335

Symptoms via clinical synopsis from OMIM:

56
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

MGI Mouse Phenotypes related to Myopathy, Centronuclear, 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.73 BIN1 DNM2 MTM1 MTMR14 MYOD1 RYR1
2 homeostasis/metabolism MP:0005376 9.7 BIN1 DNM2 MTM1 MTMR14 MYF6 MYOD1
3 muscle MP:0005369 9.5 BIN1 DNM2 MTM1 MTMR14 MYF6 MYOD1
4 respiratory system MP:0005388 8.92 MTM1 MYF6 MYOD1 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 29 DNM2 MTMR14
2 Centronuclear Myopathy, Autosomal, Modifier of 29

Anatomical Context for Myopathy, Centronuclear, 1

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

40
Eye, Skeletal Muscle, Bone

Publications for Myopathy, Centronuclear, 1

Articles related to Myopathy, Centronuclear, 1:

(show all 15)
# Title Authors PMID Year
1
A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy. 56 6
17008356 2006
2
Mutations in dynamin 2 cause dominant centronuclear myopathy. 56 6
16227997 2005
3
Clinical utility gene card for: Centronuclear and myotubular myopathies. 6
22617344 2012
4
Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy. 56
22396310 2012
5
A new centronuclear myopathy phenotype due to a novel dynamin 2 mutation. 56
19122038 2009
6
Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset. 56
17932957 2007
7
Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy. 6
11053684 2000
8
The myotubular myopathies: differential diagnosis of the X linked recessive, autosomal dominant, and autosomal recessive forms and present state of DNA studies. 56
8544184 1995
9
Fetus-like dystrophin expression and other cytoskeletal protein abnormalities in centronuclear myopathies. 56
7935525 1994
10
[Centronuclear myopathy with autosomal dominant inheritance(author's transl)]. 56
1150240 1975
11
Centronuclear myopathy with autosomal dominant inheritance. 56
5016690 1972
12
Type I muscle fibre atrophy and central nuclei. A rare familial neuromuscular disease. 56
4910660 1970
13
Myotubular myopathy. Persistence of fetal muscle in an adolescent boy. 56
4954227 1966
14
Bio-economic and operational feasibility of introducing oestrus synchronization and artificial insemination in simulated smallholder sheep breeding programmes. 61
29143721 2018
15
DNM2 mutations in Chinese Han patients with centronuclear myopathy. 61
26908122 2016

Variations for Myopathy, Centronuclear, 1

ClinVar genetic disease variations for Myopathy, Centronuclear, 1:

6 (show all 15) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DNM2 NM_001005360.2(DNM2):c.1565G>A (p.Arg522His)SNV Pathogenic 158514 rs587783595 19:10922947-10922947 19:10812271-10812271
2 DNM2 NM_001005360.2(DNM2):c.1106G>A (p.Arg369Gln)SNV Pathogenic 7279 rs121909089 19:10904509-10904509 19:10793833-10793833
3 DNM2 NM_001005360.2(DNM2):c.1105C>T (p.Arg369Trp)SNV Pathogenic 7280 rs121909090 19:10904508-10904508 19:10793832-10793832
4 DNM2 NM_001005360.2(DNM2):c.1393C>T (p.Arg465Trp)SNV Pathogenic 7281 rs121909091 19:10909219-10909219 19:10798543-10798543
5 DNM2 NM_001005360.2(DNM2):c.1102G>A (p.Glu368Lys)SNV Pathogenic 7282 rs121909092 19:10904505-10904505 19:10793829-10793829
6 MYOD1 NM_002478.5(MYOD1):c.557dup (p.Arg188fs)duplication Pathogenic 631486 11:17741881-17741882 11:17720334-17720335
7 DNM2 NM_001005360.2(DNM2):c.1856C>T (p.Ser619Leu)SNV Pathogenic/Likely pathogenic 7285 rs121909095 19:10934538-10934538 19:10823862-10823862
8 DNM2 NM_001005360.2(DNM2):c.2179C>T (p.His727Tyr)SNV Conflicting interpretations of pathogenicity 327987 rs142963320 19:10939832-10939832 19:10829156-10829156
9 DNM2 NM_001005360.2(DNM2):c.1090C>T (p.Arg364Cys)SNV Uncertain significance 560989 rs1568304333 19:10904493-10904493 19:10793817-10793817
10 DNM2 NM_001005360.2(DNM2):c.197G>A (p.Arg66Gln)SNV Uncertain significance 562194 rs1568283807 19:10870449-10870449 19:10759773-10759773
11 MTMR14 NM_001077525.3(MTMR14):c.1790G>A (p.Arg597Gln)SNV Uncertain significance 619283 rs757795544 3:9743494-9743494 3:9701810-9701810
12 MYF6 NM_002469.3(MYF6):c.334G>T (p.Ala112Ser)SNV Uncertain significance 14153 rs28928909 12:81101832-81101832 12:80708053-80708053
13 MTM1 NM_000252.2(MTM1):c.1533C>A (p.Asn511Lys)SNV Uncertain significance 634542 rs1569565536 X:149831971-149831971 X:150663498-150663498
14 DNM2 NM_001005360.2(DNM2):c.1810G>A (p.Glu604Lys)SNV Uncertain significance 694734 19:10934492-10934492 19:10823816-10823816
15 MYF6 NM_002469.3(MYF6):c.269C>A (p.Ala90Asp)SNV Benign/Likely benign 472752 rs138296448 12:81101767-81101767 12:80707988-80707988

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

73 (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 rs155571586
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

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 11.23 DNM2 BIN1
2 11.05 MYOD1 MYF6
3
Show member pathways
10.72 MYOD1 MYF6
4 10.27 DNM2 BIN1

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 ruffle GO:0001726 9.16 MTMR14 MTM1
2 T-tubule GO:0030315 8.96 RYR1 BIN1
3 I band GO:0031674 8.8 RYR1 MTM1 BIN1

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

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.78 RYR1 MYOD1 MYF6 BIN1
2 peptidyl-tyrosine dephosphorylation GO:0035335 9.51 MTMR14 MTM1
3 phosphatidylinositol biosynthetic process GO:0006661 9.49 MTMR14 MTM1
4 skeletal muscle tissue development GO:0007519 9.46 MYOD1 MYF6
5 skeletal muscle cell differentiation GO:0035914 9.43 MYOD1 MYF6
6 endosome to lysosome transport GO:0008333 9.4 MTM1 BIN1
7 positive regulation of muscle cell differentiation GO:0051149 9.37 MYOD1 MYF6
8 skeletal muscle fiber development GO:0048741 9.32 RYR1 MYOD1
9 positive regulation of myoblast differentiation GO:0045663 9.26 MYOD1 MYF6
10 positive regulation of myoblast fusion GO:1901741 9.16 MYOD1 MYF6
11 positive regulation of skeletal muscle fiber development GO:0048743 8.96 MYOD1 MYF6
12 muscle cell fate commitment GO:0042693 8.62 MYOD1 MYF6

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

# Name GO ID Score Top Affiliating Genes
1 enzyme binding GO:0019899 9.33 RYR1 MYOD1 DNM2
2 E-box binding GO:0070888 8.96 MYOD1 MYF6
3 phosphatidylinositol-3-phosphatase activity GO:0004438 8.62 MTMR14 MTM1

Sources for Myopathy, Centronuclear, 1

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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