MFM2
MCID: MYP082
MIFTS: 41

Myopathy, Myofibrillar, 2 (MFM2)

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

Aliases & Classifications for Myopathy, Myofibrillar, 2

MalaCards integrated aliases for Myopathy, Myofibrillar, 2:

Name: Myopathy, Myofibrillar, 2 56 73
Alpha-B Crystallinopathy 56 12 73 29 6 71
Myopathy, Myofibrillar, Alpha-B Crystallin-Related 56 13
Myofibrillar Myopathy 2 12 15
Mfm2 56 73
Myopathy, Myofibrillar, with or Without Cataract and/or Cardiomyopathy 56
Myopathy, Desmin-Related, Associated with Mutation in the Cryab Gene 56
Myofibrillar Myopathy with or Without Cataract and/or Cardiomyopathy 73
Myopathy Desmin-Related Associated with Mutation in the Cryab Gene 73
Alpha-B Crystallin-Related Late-Onset Distal Myopathy 58
Myopathy Cardioskeletal Desmin-Related with Cataract 73
Myofibrillar Myopathy Alpha-B Crystallin-Related 73
Alpha-B Crystallin-Related Late-Onset Myopathy 58
Alpha-B Crystallinopathy with Cataract 73
Desmin-Related Myopathy with Cataract 73
Late-Onset Distal Crystallinopathy 58
Mfm Alpha-B Crystallin-Related 73
Myopathy, Myofibrillar, Type 2 39

Characteristics:

OMIM:

56
Miscellaneous:
adult onset
slowly progressive
clinical variability
two patients without cardiomyopathy or cataracts have been reported

Inheritance:
autosomal dominant


HPO:

31
myopathy, myofibrillar, 2:
Inheritance autosomal dominant inheritance
Onset and clinical course adult onset slow progression


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0080093
OMIM 56 608810
OMIM Phenotypic Series 56 PS601419
MeSH 43 D020914
ICD10 via Orphanet 33 G71.0
Orphanet 58 ORPHA399058
MedGen 41 C1837317
UMLS 71 C1837317

Summaries for Myopathy, Myofibrillar, 2

OMIM : 56 Alpha-B crystallin-related myofibrillar myopathy is an autosomal dominant muscular disorder characterized by adult onset of progressive muscle weakness affecting both the proximal and distal muscles and associated with respiratory insufficiency, cardiomyopathy, and cataracts. There is phenotypic variability both within and between families (Fardeau et al., 1978; Selcen and Engel, 2003). A homozygous founder mutation in the CRYAB gene has been identified in Canadian aboriginal infants of Cree origin who have a severe fatal infantile hypertonic form of myofibrillar myopathy; see 613869. For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419). (608810)

MalaCards based summary : Myopathy, Myofibrillar, 2, also known as alpha-b crystallinopathy, is related to early-onset lamellar cataract and cataract 16, multiple types. An important gene associated with Myopathy, Myofibrillar, 2 is CRYAB (Crystallin Alpha B). Related phenotypes are dysphagia and dysphonia

Disease Ontology : 12 A myofibrillar myopathy that has material basis in heterozygous mutation in the alpha-B-crystallin gene on chromosome 11q23.

UniProtKB/Swiss-Prot : 73 Myopathy, myofibrillar, 2: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM2 is characterized by weakness of the proximal and distal limb muscles, weakness of the neck, velopharynx and trunk muscles, hypertrophic cardiomyopathy, and cataract in a subset of patients.

Related Diseases for Myopathy, Myofibrillar, 2

Diseases in the Myofibrillar Myopathy family:

Myopathy, Myofibrillar, 1 Myopathy, Myofibrillar, 2
Myopathy, Myofibrillar, 3 Myopathy, Myofibrillar, 4
Myopathy, Myofibrillar, 5 Myopathy, Myofibrillar, 6
Myopathy, Myofibrillar, 7 Myopathy, Myofibrillar, 8

Diseases related to Myopathy, Myofibrillar, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 67)
# Related Disease Score Top Affiliating Genes
1 early-onset lamellar cataract 10.4 CRYAB CRYAA
2 cataract 16, multiple types 10.4 CRYAB CRYAA
3 muscular dystrophy, limb-girdle, type 1h 10.3 MYOT DNAJB6
4 early-onset nuclear cataract 10.3 CRYAB CRYAA
5 muscular dystrophy-dystroglycanopathy , type c, 9 10.3 MYOT DNAJB6
6 fatal infantile hypertonic myofibrillar myopathy 10.3 SYNPO2 CRYAB
7 muscular dystrophy, limb-girdle, autosomal dominant 3 10.2 MYOT DNAJB6
8 neuronopathy, distal hereditary motor, type iic 10.2 HSPB8 CRYAB
9 posterior polar cataract 10.2 CRYAB CRYAA
10 giant axonal neuropathy 2 10.2 HSPB8 BAG3
11 muscular dystrophy, limb-girdle, autosomal dominant 2 10.2 MYOT DNAJB6
12 neuronopathy, distal hereditary motor, type iia 10.2 HSPB8 CRYAA
13 myopathy, myofibrillar, 6 10.2 HSPB8 BAG3
14 charcot-marie-tooth disease, axonal, type 2l 10.1 HSPB8 CRYAA
15 scapuloperoneal syndrome, neurogenic, kaeser type 10.1 SELENON MYOT
16 central core disease of muscle 10.0 SELENON MYOT
17 alexander disease 10.0 PLEC CRYAB CRYAA
18 myopathy, centronuclear, 1 10.0 MYOT FLNC DNAJB6
19 hyaline body myopathy 10.0 SELENON MYOT
20 autosomal dominant distal myopathy 10.0 MYOT DMD
21 epithelial basement membrane dystrophy 9.9 SYNC PLEC
22 muscular dystrophy, limb-girdle, autosomal recessive 7 9.9 MYOT DMD
23 distal hereditary motor neuronopathy type 2 9.9 HSPB8 CRYAA
24 autosomal recessive limb-girdle muscular dystrophy type 2c 9.9 MYOT DMD
25 autosomal recessive limb-girdle muscular dystrophy type 2f 9.9 MYOT DMD
26 reducing body myopathy 1a 9.9 MYOT LDB3 FLNC BAG3
27 myopathy, spheroid body 9.9 MYOT LDB3 FLNC BAG3
28 epidermolysis bullosa simplex with muscular dystrophy 9.9 SYNC PLEC
29 congenital structural myopathy 9.9 SELENON MYOT
30 autosomal recessive limb-girdle muscular dystrophy type 2a 9.8 MYOT DMD
31 autosomal dominant limb-girdle muscular dystrophy 9.8 MYOT FLNC DNAJB6 BAG3
32 autosomal recessive limb-girdle muscular dystrophy type 2b 9.8 MYOT DMD
33 muscular disease 9.8 MYOT DMD CRYAA
34 autosomal recessive limb-girdle muscular dystrophy type 2d 9.8 MYOT DMD
35 atrial standstill 1 9.8 MYOT DMD CRYAB
36 myopathy, myofibrillar, 4 9.7 MYOT LDB3 FLNC CRYAB BAG3
37 autosomal recessive limb-girdle muscular dystrophy 9.6 PLEC MYOT DMD
38 muscular dystrophy, becker type 9.6 SYNC MYOT DMD
39 autosomal recessive limb-girdle muscular dystrophy type 2q 9.6 SYNC PLEC MYOT DNAJB6
40 muscular dystrophy, limb-girdle, autosomal dominant 1 9.5 MYOT HSPB8 DNAJB6 CRYAA BAG3
41 familial isolated dilated cardiomyopathy 9.5 LDB3 DMD CRYAB BAG3
42 tibial muscular dystrophy 9.5 MYOT LDB3 FLNC DMD
43 emery-dreifuss muscular dystrophy 2, autosomal dominant 9.5 SELENON MYOT DMD
44 isolated elevated serum creatine phosphokinase levels 9.5 SELENON MYOT DMD
45 restrictive cardiomyopathy 9.5 FLNC DMD CRYAB BAG3
46 congenital fiber-type disproportion 9.5 SELENON MYOT DMD
47 ullrich congenital muscular dystrophy 1 9.5 SELENON DMD CRYAA
48 muscular dystrophy, congenital merosin-deficient, 1a 9.5 SELENON DMD
49 myopathy, myofibrillar, 9, with early respiratory failure 9.4 MYOT LDB3 FLNC DNAJB6 CRYAB BAG3
50 bethlem myopathy 1 9.3 SELENON MYOT DMD CRYAA

Graphical network of the top 20 diseases related to Myopathy, Myofibrillar, 2:



Diseases related to Myopathy, Myofibrillar, 2

Symptoms & Phenotypes for Myopathy, Myofibrillar, 2

Human phenotypes related to Myopathy, Myofibrillar, 2:

58 31 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002015
2 dysphonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001618
3 progressive distal muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0009063
4 emg: myopathic abnormalities 58 31 frequent (33%) Frequent (79-30%) HP:0003458
5 hyporeflexia 58 31 frequent (33%) Frequent (79-30%) HP:0001265
6 increased variability in muscle fiber diameter 58 31 frequent (33%) Frequent (79-30%) HP:0003557
7 foot dorsiflexor weakness 58 31 frequent (33%) Frequent (79-30%) HP:0009027
8 axial muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003327
9 neck muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0000467
10 autophagic vacuoles 58 31 frequent (33%) Frequent (79-30%) HP:0003736
11 muscle fiber inclusion bodies 58 31 frequent (33%) Frequent (79-30%) HP:0100299
12 limb-girdle muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003325
13 accumulation of muscle fiber desmin 58 31 frequent (33%) Frequent (79-30%) HP:0030225
14 posterior capsular cataract 58 31 frequent (33%) Frequent (79-30%) HP:0100020
15 abnormal circulating creatine kinase concentration 31 frequent (33%) HP:0040081
16 respiratory insufficiency due to muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0002747
17 muscle stiffness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003552
18 progressive proximal muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0009073
19 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
20 difficulty walking 58 31 occasional (7.5%) Occasional (29-5%) HP:0002355
21 facial diplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001349
22 cataract 31 HP:0000518
23 hypertrophic cardiomyopathy 31 HP:0001639
24 elevated serum creatine kinase 31 HP:0003236
25 abnormal levels of creatine kinase in blood 58 Frequent (79-30%)
26 muscular dystrophy 31 HP:0003560
27 distal muscle weakness 31 HP:0002460
28 late-onset proximal muscle weakness 31 HP:0003694
29 muscle fiber splitting 31 HP:0003555
30 decreased achilles reflex 31 HP:0009072

Symptoms via clinical synopsis from OMIM:

56
Respiratory:
respiratory insufficiency due to muscle weakness

Head And Neck Eyes:
cataracts

Cardiovascular Heart:
cardiomyopathy, hypertrophic

Muscle Soft Tissue:
neck muscle weakness
autophagic vacuoles
limb-girdle muscle weakness
foot drop
myopathic changes seen on emg
more
Laboratory Abnormalities:
increased serum creatine kinase

Clinical features from OMIM:

608810

MGI Mouse Phenotypes related to Myopathy, Myofibrillar, 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.81 BAG3 CRYAB DMD FLNC HSPB8 LDB3
2 muscle MP:0005369 9.61 BAG3 CRYAB DMD FLNC HSPB8 LDB3
3 respiratory system MP:0005388 9.1 BAG3 DMD FLNC HSPB8 LDB3 SELENON

Drugs & Therapeutics for Myopathy, Myofibrillar, 2

Search Clinical Trials , NIH Clinical Center for Myopathy, Myofibrillar, 2

Genetic Tests for Myopathy, Myofibrillar, 2

Genetic tests related to Myopathy, Myofibrillar, 2:

# Genetic test Affiliating Genes
1 Alpha-B Crystallinopathy 29 CRYAB

Anatomical Context for Myopathy, Myofibrillar, 2

Publications for Myopathy, Myofibrillar, 2

Articles related to Myopathy, Myofibrillar, 2:

(show all 16)
# Title Authors PMID Year
1
A novel CRYAB mutation resulting in multisystemic disease. 56 6
21920752 2012
2
Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. 56 6
14681890 2003
3
A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. 56 6
9731540 1998
4
[A new familial muscular disorder demonstrated by the intra-sarcoplasmic accumulation of a granulo-filamentous material which is dense on electron microscopy (author's transl)]. 56 6
570292 1978
5
Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. 6
26542570 2015
6
Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the guideline development subcommittee of the American Academy of Neurology and the practice issues review panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. 6
25313375 2014
7
BAG3-related myofibrillar myopathy in a Chinese family. 6
21361913 2012
8
Infantile muscular dystrophy in Canadian aboriginals is an αB-crystallinopathy. 6
21337604 2011
9
Alpha B-crystallin mutation in dilated cardiomyopathy. 6
16483541 2006
10
Myofibrillar Myopathy – ARCHIVED CHAPTER, FOR HISTORICAL REFERENCE ONLY 6
20301672 2005
11
Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant. 6
12812987 2003
12
Alteration of protein-protein interactions of congenital cataract crystallin mutants. 6
12601044 2003
13
Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy. 56
8792816 1996
14
Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives. 6
8000975 1994
15
Mapping of additional markers in fission yeast, especially fus1 and three mfm genes. 61
8001176 1994
16
Analysis of the structural genes encoding M-factor in the fission yeast Schizosaccharomyces pombe: identification of a third gene, mfm3. 61
8196631 1994

Variations for Myopathy, Myofibrillar, 2

ClinVar genetic disease variations for Myopathy, Myofibrillar, 2:

6 (show all 15) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CRYAB NM_001289808.2(CRYAB):c.358A>G (p.Arg120Gly)SNV Pathogenic 16953 rs104894201 11:111779658-111779658 11:111908934-111908934
2 CRYAB NM_001289808.2(CRYAB):c.464_465del (p.Pro155fs)deletion Pathogenic 16955 rs1566402514 11:111779551-111779552 11:111908827-111908828
3 CRYAB NM_001289808.2(CRYAB):c.451C>T (p.Gln151Ter)SNV Pathogenic 16956 rs104894202 11:111779565-111779565 11:111908841-111908841
4 CRYAB NM_001289808.2(CRYAB):c.60del (p.Ser21fs)deletion Pathogenic 29669 rs281865141 11:111782389-111782389 11:111911665-111911665
5 CRYAB NM_001289808.2(CRYAB):c.325G>C (p.Asp109His)SNV Pathogenic 41930 rs387907339 11:111779691-111779691 11:111908967-111908967
6 CRYAB NM_001289808.2(CRYAB):c.343del (p.Ser115fs)deletion Pathogenic/Likely pathogenic 38963 rs281865142 11:111779673-111779673 11:111908949-111908949
7 CRYAB NM_001289808.2(CRYAB):c.152C>T (p.Pro51Leu)SNV Conflicting interpretations of pathogenicity 44232 rs2234704 11:111782297-111782297 11:111911573-111911573
8 CRYAB NM_001289808.2(CRYAB):c.116C>T (p.Pro39Leu)SNV Conflicting interpretations of pathogenicity 178013 rs149787233 11:111782333-111782333 11:111911609-111911609
9 CRYAB NM_001289808.2(CRYAB):c.*38G>CSNV Conflicting interpretations of pathogenicity 302430 rs781853968 11:111779450-111779450 11:111908726-111908726
10 CRYAB NM_001289808.2(CRYAB):c.*39T>CSNV Uncertain significance 302429 rs782808506 11:111779449-111779449 11:111908725-111908725
11 CRYAB NM_001289808.2(CRYAB):c.115C>G (p.Pro39Ala)SNV Uncertain significance 571646 rs145768025 11:111782334-111782334 11:111911610-111911610
12 CRYAB NM_001289808.2(CRYAB):c.482T>C (p.Ile161Thr)SNV Uncertain significance 810752 11:111779534-111779534 11:111908810-111908810
13 CRYAB NM_001289808.2(CRYAB):c.*60G>ASNV Uncertain significance 877466 11:111779428-111779428 11:111908704-111908704
14 CRYAB NM_001289808.2(CRYAB):c.176G>A (p.Ser59Asn)SNV Uncertain significance 879070 11:111782273-111782273 11:111911549-111911549
15 CRYAB NM_001289808.2(CRYAB):c.60C>T (p.Pro20=)SNV Benign 44239 rs4252582 11:111782389-111782389 11:111911665-111911665

UniProtKB/Swiss-Prot genetic disease variations for Myopathy, Myofibrillar, 2:

73
# Symbol AA change Variation ID SNP ID
1 CRYAB p.Arg120Gly VAR_007899 rs104894201
2 CRYAB p.Asp109His VAR_069528 rs387907339

Expression for Myopathy, Myofibrillar, 2

Search GEO for disease gene expression data for Myopathy, Myofibrillar, 2.

Pathways for Myopathy, Myofibrillar, 2

GO Terms for Myopathy, Myofibrillar, 2

Cellular components related to Myopathy, Myofibrillar, 2 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 10.1 SYNPO2 SYNC PLEC HSPB8 FLNC DNAJB6
2 cytoplasm GO:0005737 10.03 SYNPO2 SYNC PLEC MYOT LDB3 HSPB8
3 cytoskeleton GO:0005856 9.95 SYNPO2 PLEC MYOT LDB3 FLNC DMD
4 perinuclear region of cytoplasm GO:0048471 9.83 SYNC PLEC LDB3 DNAJB6 DMD
5 stress fiber GO:0001725 9.5 SYNPO2 LDB3 BAG3
6 contractile fiber GO:0043292 9.49 PLEC CRYAB
7 chaperone complex GO:0101031 9.46 HSPB8 BAG3
8 sarcoplasm GO:0016528 9.37 PLEC FLNC
9 sarcolemma GO:0042383 9.35 SYNC PLEC MYOT FLNC DMD
10 costamere GO:0043034 9.33 PLEC FLNC DMD
11 Z disc GO:0030018 9.28 SYNPO2 SYNC MYOT LDB3 FLNC DNAJB6

Biological processes related to Myopathy, Myofibrillar, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein stabilization GO:0050821 9.65 CRYAB CRYAA BAG3
2 protein folding GO:0006457 9.61 DNAJB6 CRYAB BAG3
3 cellular response to unfolded protein GO:0034620 9.46 HSPB8 BAG3
4 muscle cell cellular homeostasis GO:0046716 9.4 DMD BAG3
5 muscle fiber development GO:0048747 9.37 FLNC DMD
6 regulation of ryanodine-sensitive calcium-release channel activity GO:0060314 9.32 SELENON DMD
7 chaperone-mediated autophagy GO:0061684 9.26 SYNPO2 BAG3
8 positive regulation of aggrephagy GO:1905337 9.16 HSPB8 BAG3
9 negative regulation of intracellular transport GO:0032387 8.96 CRYAB CRYAA
10 regulation of cellular response to heat GO:1900034 8.92 HSPB8 DNAJB6 CRYAB BAG3

Molecular functions related to Myopathy, Myofibrillar, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 structural molecule activity GO:0005198 9.63 PLEC CRYAB CRYAA
2 unfolded protein binding GO:0051082 9.5 DNAJB6 CRYAB CRYAA
3 structural constituent of eye lens GO:0005212 9.43 CRYAB CRYAA
4 ankyrin binding GO:0030506 9.4 PLEC FLNC
5 muscle alpha-actinin binding GO:0051371 9.37 SYNPO2 LDB3
6 structural constituent of muscle GO:0008307 9.33 PLEC MYOT DMD
7 alpha-actinin binding GO:0051393 9.26 SYNPO2 MYOT
8 cytoskeletal protein binding GO:0008092 9.26 PLEC LDB3 FLNC CRYAB
9 actin binding GO:0003779 9.1 SYNPO2 PLEC MYOT LDB3 FLNC DMD

Sources for Myopathy, Myofibrillar, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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29 GTR
30 HMDB
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32 ICD10
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48 NCI
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50 NDF-RT
53 NINDS
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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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