MFM2
MCID: MYP082
MIFTS: 40

Myopathy, Myofibrillar, 2 (MFM2)

Categories: Cancer diseases, Cardiovascular diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Oral diseases, Rare diseases, Respiratory diseases, Smell/Taste diseases

Aliases & Classifications for Myopathy, Myofibrillar, 2

MalaCards integrated aliases for Myopathy, Myofibrillar, 2:

Name: Myopathy, Myofibrillar, 2 57 72
Alpha-B Crystallinopathy 57 12 72 29 6 70
Myopathy, Myofibrillar, Alpha-B Crystallin-Related 57 13
Myofibrillar Myopathy 2 12 15
Mfm2 57 72
Myopathy, Myofibrillar, with or Without Cataract and/or Cardiomyopathy 57
Myopathy, Desmin-Related, Associated with Mutation in the Cryab Gene 57
Myofibrillar Myopathy with or Without Cataract and/or Cardiomyopathy 72
Myopathy Desmin-Related Associated with Mutation in the Cryab Gene 72
Alpha-B Crystallin-Related Late-Onset Distal Myopathy 58
Myopathy Cardioskeletal Desmin-Related with Cataract 72
Myofibrillar Myopathy Alpha-B Crystallin-Related 72
Alpha-B Crystallin-Related Late-Onset Myopathy 58
Alpha-B Crystallinopathy with Cataract 72
Desmin-Related Myopathy with Cataract 72
Late-Onset Distal Crystallinopathy 58
Mfm Alpha-B Crystallin-Related 72
Myopathy, Myofibrillar, Type 2 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
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® 57 608810
OMIM Phenotypic Series 57 PS601419
MeSH 44 D020914
ICD10 via Orphanet 33 G71.0
Orphanet 58 ORPHA399058
MedGen 41 C1837317
UMLS 70 C1837317

Summaries for Myopathy, Myofibrillar, 2

OMIM® : 57 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) (Updated 05-Apr-2021)

MalaCards based summary : Myopathy, Myofibrillar, 2, also known as alpha-b crystallinopathy, is related to early-onset lamellar cataract and limb-girdle muscular dystrophy type 1a. An important gene associated with Myopathy, Myofibrillar, 2 is CRYAB (Crystallin Alpha B). Related phenotypes are dysphonia and dysphagia

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 : 72 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
Myofibrillar Myopathy 10 Myofibrillar Myopathy 11

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

(show top 50) (show all 60)
# Related Disease Score Top Affiliating Genes
1 early-onset lamellar cataract 10.3 CRYAB CRYAA
2 limb-girdle muscular dystrophy type 1a 10.2 MYOT FLNC
3 presbyopia 10.2 CRYAB CRYAA
4 muscular dystrophy, limb-girdle, type 1h 10.2 MYOT DNAJB6
5 cataract 16, multiple types 10.2 CRYAB CRYAA
6 autosomal recessive limb-girdle muscular dystrophy type 2a 10.2 MYOT FLNC
7 posterior polar cataract 10.2 CRYAB CRYAA
8 muscular dystrophy, limb-girdle, autosomal dominant 3 10.2 MYOT DNAJB6
9 neuronopathy, distal hereditary motor, type iic 10.2 HSPB8 CRYAB
10 muscular dystrophy, limb-girdle, autosomal dominant 2 10.2 MYOT DNAJB6
11 early-onset nuclear cataract 10.2 CRYAB CRYAA
12 neuronopathy, distal hereditary motor, type iia 10.1 HSPB8 CRYAA
13 mitochondrial dna depletion syndrome 12b 10.1 FLNC BAG3
14 charcot-marie-tooth disease, axonal, type 2l 10.1 HSPB8 CRYAA
15 central core disease of muscle 10.1 SELENON MYOT
16 myopathy, myofibrillar, 6 10.1 HSPB8 BAG3
17 muscular disease 10.1 MYOT FLNC CRYAA
18 tibial muscular dystrophy 10.1 MYOT LDB3 FLNC
19 giant axonal neuropathy 2 10.1 HSPB8 BAG3
20 xanthomatosis 10.0 FLNC CRYAA
21 distal hereditary motor neuronopathy type 2 10.0 HSPB8 CRYAA
22 cerebrotendinous xanthomatosis 10.0 FLNC CRYAA
23 myopathy, centronuclear, 1 10.0 MYOT FLNC DNAJB6
24 scapuloperoneal syndrome, neurogenic, kaeser type 10.0 SELENON MYOT LDB3
25 atrial standstill 1 10.0 MYOT FLNC CRYAB
26 alexander disease 10.0 PLEC CRYAB CRYAA
27 miyoshi muscular dystrophy 10.0 MYOT HSPB8 FLNC
28 fatal infantile hypertonic myofibrillar myopathy 10.0 SYNPO2 CRYAB
29 autosomal recessive limb-girdle muscular dystrophy 10.0 PLEC MYOT FLNC
30 hyaline body myopathy 10.0 SELENON MYOT FLNC
31 congenital structural myopathy 10.0 SELENON MYOT FLNC
32 bethlem myopathy 1 10.0 SELENON MYOT CRYAA
33 emery-dreifuss muscular dystrophy 10.0 PLEC MYOT LDB3
34 spinal and bulbar muscular atrophy, x-linked 1 10.0 HSPB8 CRYAA BAG3
35 epithelial basement membrane dystrophy 9.9 SYNC PLEC
36 myopathy, spheroid body 9.9 MYOT LDB3 FLNC BAG3
37 restrictive cardiomyopathy 9.9 LDB3 FLNC CRYAB BAG3
38 left ventricular noncompaction 9.9 MYOT LDB3 FLNC BAG3
39 nonaka myopathy 9.9 MYOT LDB3 FLNC DNAJB6
40 cardiomyopathy, dilated, 1a 9.8 MYOT BAG3
41 epidermolysis bullosa simplex with muscular dystrophy 9.8 SYNC PLEC
42 autosomal dominant limb-girdle muscular dystrophy 9.8 MYOT FLNC DNAJB6 BAG3
43 muscle tissue disease 9.8 SELENON MYOT FLNC CRYAA
44 rigid spine muscular dystrophy 1 9.8 SELENON MYOT LDB3 BAG3
45 arrhythmogenic right ventricular cardiomyopathy 9.8 PLEC LDB3 FLNC
46 walker-warburg syndrome 9.8 SELENON PLEC MYOT
47 myopathy, myofibrillar, 4 9.8 MYOT LDB3 FLNC CRYAB BAG3
48 muscular dystrophy, limb-girdle, autosomal dominant 1 9.6 MYOT HSPB8 DNAJB6 CRYAA BAG3
49 autosomal recessive limb-girdle muscular dystrophy type 2q 9.6 SYNC PLEC MYOT DNAJB6
50 hypertrophic cardiomyopathy 9.6 LDB3 FLNC CRYAB BAG3

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 dysphonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001618
2 dysphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002015
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®:

57 (Updated 05-Apr-2021)
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 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Myopathy, Myofibrillar, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.23 BAG3 CRYAB FLNC HSPB8 LDB3 PLEC

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 14)
# Title Authors PMID Year
1
A novel CRYAB mutation resulting in multisystemic disease. 57 6
21920752 2012
2
Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. 6 57
14681890 2003
3
A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. 57 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)]. 6 57
570292 1978
5
A novel dominant mutation in CRYAB gene leading to a severe phenotype with childhood onset. 6
32420686 2020
6
Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. 6
26542570 2015
7
Infantile muscular dystrophy in Canadian aboriginals is an αB-crystallinopathy. 6
21337604 2011
8
Alpha B-crystallin mutation in dilated cardiomyopathy. 6
16483541 2006
9
Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant. 6
12812987 2003
10
Alteration of protein-protein interactions of congenital cataract crystallin mutants. 6
12601044 2003
11
Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy. 57
8792816 1996
12
Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives. 6
8000975 1994
13
Mapping of additional markers in fission yeast, especially fus1 and three mfm genes. 61
8001176 1994
14
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 17)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CRYAB NM_001289808.2(CRYAB):c.358A>G (p.Arg120Gly) SNV Pathogenic 16953 rs104894201 GRCh37: 11:111779658-111779658
GRCh38: 11:111908934-111908934
2 CRYAB NM_001289808.2(CRYAB):c.464_465del (p.Pro155fs) Deletion Pathogenic 16955 rs1566402514 GRCh37: 11:111779551-111779552
GRCh38: 11:111908827-111908828
3 CRYAB NM_001289808.2(CRYAB):c.451C>T (p.Gln151Ter) SNV Pathogenic 16956 rs104894202 GRCh37: 11:111779565-111779565
GRCh38: 11:111908841-111908841
4 CRYAB NM_001289808.2(CRYAB):c.325G>C (p.Asp109His) SNV Pathogenic 41930 rs387907339 GRCh37: 11:111779691-111779691
GRCh38: 11:111908967-111908967
5 CRYAB NM_001289808.2(CRYAB):c.60del (p.Ser21fs) Deletion Pathogenic 29669 rs281865141 GRCh37: 11:111782389-111782389
GRCh38: 11:111911665-111911665
6 CRYAB NM_001289808.2(CRYAB):c.514del (p.Ala172fs) Deletion Pathogenic 804222 GRCh37: 11:111779502-111779502
GRCh38: 11:111908778-111908778
7 CRYAB NM_001289808.2(CRYAB):c.343del (p.Ser115fs) Deletion Pathogenic 38963 rs281865142 GRCh37: 11:111779673-111779673
GRCh38: 11:111908949-111908949
8 CRYAB NM_001289808.2(CRYAB):c.519del (p.Lys174fs) Deletion Uncertain significance 1032782 GRCh37: 11:111779497-111779497
GRCh38: 11:111908773-111908773
9 CRYAB NM_001289808.2(CRYAB):c.*39T>C SNV Uncertain significance 302429 rs782808506 GRCh37: 11:111779449-111779449
GRCh38: 11:111908725-111908725
10 CRYAB NM_001289808.2(CRYAB):c.115C>G (p.Pro39Ala) SNV Uncertain significance 571646 rs145768025 GRCh37: 11:111782334-111782334
GRCh38: 11:111911610-111911610
11 CRYAB NM_001289808.2(CRYAB):c.*60G>A SNV Uncertain significance 877466 GRCh37: 11:111779428-111779428
GRCh38: 11:111908704-111908704
12 CRYAB NM_001289808.2(CRYAB):c.482T>C (p.Ile161Thr) SNV Uncertain significance 810752 rs1592506005 GRCh37: 11:111779534-111779534
GRCh38: 11:111908810-111908810
13 CRYAB NM_001289808.2(CRYAB):c.176G>A (p.Ser59Asn) SNV Uncertain significance 879070 GRCh37: 11:111782273-111782273
GRCh38: 11:111911549-111911549
14 CRYAB NM_001289808.2(CRYAB):c.*38G>C SNV Benign 302430 rs781853968 GRCh37: 11:111779450-111779450
GRCh38: 11:111908726-111908726
15 CRYAB NM_001289808.2(CRYAB):c.60C>T (p.Pro20=) SNV Benign 44239 rs4252582 GRCh37: 11:111782389-111782389
GRCh38: 11:111911665-111911665
16 CRYAB NM_001289808.2(CRYAB):c.152C>T (p.Pro51Leu) SNV Benign 44232 rs2234704 GRCh37: 11:111782297-111782297
GRCh38: 11:111911573-111911573
17 CRYAB NM_001289808.2(CRYAB):c.116C>T (p.Pro39Leu) SNV Benign 178013 rs149787233 GRCh37: 11:111782333-111782333
GRCh38: 11:111911609-111911609

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

72
# 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 10.11 SYNPO2 SYNC PLEC HSPB8 FLNC DNAJB6
2 cytoplasm GO:0005737 10 SYNPO2 SYNC PLEC MYOT LDB3 HSPB8
3 cytoskeleton GO:0005856 9.89 SYNPO2 PLEC MYOT LDB3 FLNC
4 perinuclear region of cytoplasm GO:0048471 9.78 SYNC PLEC LDB3 DNAJB6
5 costamere GO:0043034 9.43 PLEC FLNC
6 chaperone complex GO:0101031 9.4 HSPB8 BAG3
7 contractile fiber GO:0043292 9.37 PLEC CRYAB
8 stress fiber GO:0001725 9.33 SYNPO2 LDB3 BAG3
9 sarcoplasm GO:0016528 9.32 PLEC FLNC
10 sarcolemma GO:0042383 9.26 SYNC PLEC MYOT FLNC
11 Z disc GO:0030018 9.23 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 9.58 CRYAB CRYAA BAG3
2 protein folding GO:0006457 9.5 DNAJB6 CRYAB BAG3
3 cellular response to unfolded protein GO:0034620 9.37 HSPB8 BAG3
4 chaperone-mediated autophagy GO:0061684 9.26 SYNPO2 BAG3
5 positive regulation of aggrephagy GO:1905337 9.16 HSPB8 BAG3
6 negative regulation of intracellular transport GO:0032387 8.96 CRYAB CRYAA
7 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 9.61 PLEC CRYAB CRYAA
2 structural constituent of muscle GO:0008307 9.46 PLEC MYOT
3 structural constituent of eye lens GO:0005212 9.4 CRYAB CRYAA
4 ankyrin binding GO:0030506 9.37 PLEC FLNC
5 actin binding GO:0003779 9.35 SYNPO2 PLEC MYOT LDB3 FLNC
6 unfolded protein binding GO:0051082 9.33 DNAJB6 CRYAB CRYAA
7 alpha-actinin binding GO:0051393 9.32 SYNPO2 MYOT
8 muscle alpha-actinin binding GO:0051371 9.26 SYNPO2 LDB3
9 cytoskeletal protein binding GO:0008092 8.92 PLEC LDB3 FLNC CRYAB

Sources for Myopathy, Myofibrillar, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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