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 57 74
Alpha-B Crystallinopathy 57 12 74 29 6 72
Myopathy, Myofibrillar, Alpha-B Crystallin-Related 57 13
Myofibrillar Myopathy 2 12 15
Mfm2 57 74
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 74
Myopathy Desmin-Related Associated with Mutation in the Cryab Gene 74
Alpha-B Crystallin-Related Late-Onset Distal Myopathy 59
Myopathy Cardioskeletal Desmin-Related with Cataract 74
Myofibrillar Myopathy Alpha-B Crystallin-Related 74
Alpha-B Crystallin-Related Late-Onset Myopathy 59
Alpha-B Crystallinopathy with Cataract 74
Desmin-Related Myopathy with Cataract 74
Late-Onset Distal Crystallinopathy 59
Mfm Alpha-B Crystallin-Related 74
Myopathy, Myofibrillar, Type 2 40

Characteristics:

OMIM:

57
Miscellaneous:
adult onset
slowly progressive
clinical variability
two patients without cardiomyopathy or cataracts have been reported

Inheritance:
autosomal dominant


HPO:

32
myopathy, myofibrillar, 2:
Inheritance autosomal dominant inheritance
Onset and clinical course adult onset slow progression


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0080093
MeSH 44 D020914
ICD10 via Orphanet 34 G71.0
Orphanet 59 ORPHA399058
MedGen 42 C1837317
UMLS 72 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)

MalaCards based summary : Myopathy, Myofibrillar, 2, also known as alpha-b crystallinopathy, is related to myopathy, myofibrillar, 4 and autosomal recessive limb-girdle muscular dystrophy type 2q. An important gene associated with Myopathy, Myofibrillar, 2 is CRYAB (Crystallin Alpha B), and among its related pathways/superpathways are Apoptosis and survival Caspase cascade and Cytoskeletal Signaling. 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 : 74 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 all 24)
# Related Disease Score Top Affiliating Genes
1 myopathy, myofibrillar, 4 10.4 MYOT LDB3
2 autosomal recessive limb-girdle muscular dystrophy type 2q 10.4 PLEC MYOT
3 alexander disease 10.3 PLEC CRYAB
4 autosomal dominant limb-girdle muscular dystrophy 10.3 MYOT FLNC
5 cardiomyopathy, dilated, 1b 10.2 LDB3 DMD
6 muscular dystrophy, limb-girdle, autosomal recessive 7 10.2 MYOT DMD
7 muscular dystrophy, congenital, 1b 10.2 LDB3 DMD
8 cardiomyopathy, dilated, 1d 10.1 LDB3 DMD
9 myopathy, myofibrillar, 3 10.1 MYOT LDB3 FLNC
10 cardiomyopathy, dilated, 1a 10.1 LDB3 DMD
11 myopathy, tubular aggregate, 1 10.1 FLNC ACTA1
12 restrictive cardiomyopathy 10.0 FLNC CRYAB ACTA1
13 familial isolated dilated cardiomyopathy 10.0 LDB3 DMD CRYAB
14 miyoshi muscular dystrophy 10.0 MYOT DMD
15 myopathy, myofibrillar, 1 9.9 MYOT LDB3 FLNC CRYAB
16 myopathy, spheroid body 9.9 MYOT LDB3 FLNC CRYAB
17 rigid spine muscular dystrophy 1 9.8 DMD ACTA1
18 pick disease of brain 9.6 CRYAB APP
19 dilated cardiomyopathy 9.6 LDB3 FLNC DMD CRYAB
20 limb-girdle muscular dystrophy 9.6 PLEC MYOT FLNC DMD
21 myopathy 9.6 MYOT LDB3 FLNC CRYAB ACTA1
22 muscular dystrophy 9.3 PLEC MYOT FLNC DMD ACTA1
23 myofibrillar myopathy 9.1 MYOT LDB3 FLNC DMD CRYAB ACTA1
24 muscular disease 9.0 PLEC MYOT LDB3 FLNC DMD ACTA1

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:

59 32 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001618
2 dysphagia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002015
3 progressive distal muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0009063
4 emg: myopathic abnormalities 59 32 frequent (33%) Frequent (79-30%) HP:0003458
5 hyporeflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001265
6 axial muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0003327
7 limb-girdle muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0003325
8 increased variability in muscle fiber diameter 59 32 frequent (33%) Frequent (79-30%) HP:0003557
9 foot dorsiflexor weakness 59 32 frequent (33%) Frequent (79-30%) HP:0009027
10 neck muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0000467
11 autophagic vacuoles 59 32 frequent (33%) Frequent (79-30%) HP:0003736
12 accumulation of muscle fiber desmin 59 32 frequent (33%) Frequent (79-30%) HP:0030225
13 posterior capsular cataract 59 32 frequent (33%) Frequent (79-30%) HP:0100020
14 muscle fiber inclusion bodies 59 32 frequent (33%) Frequent (79-30%) HP:0100299
15 abnormal circulating creatine kinase concentration 32 frequent (33%) HP:0040081
16 respiratory insufficiency due to muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0002747
17 cardiomyopathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001638
18 muscle stiffness 59 32 occasional (7.5%) Occasional (29-5%) HP:0003552
19 difficulty walking 59 32 occasional (7.5%) Occasional (29-5%) HP:0002355
20 facial diplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001349
21 progressive proximal muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0009073
22 cataract 32 HP:0000518
23 hypertrophic cardiomyopathy 32 HP:0001639
24 abnormal levels of creatine kinase in blood 59 Frequent (79-30%)
25 late-onset proximal muscle weakness 32 HP:0003694
26 muscular dystrophy 32 HP:0003560
27 distal muscle weakness 32 HP:0002460
28 muscle fiber splitting 32 HP:0003555
29 decreased achilles reflex 32 HP:0009072
30 elevated serum creatine kinase 32 HP:0003236

Symptoms via clinical synopsis from OMIM:

57
Respiratory:
respiratory insufficiency due to muscle weakness

Head And Neck Eyes:
cataracts

Cardiovascular Heart:
cardiomyopathy, hypertrophic

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

Clinical features from OMIM:

608810

MGI Mouse Phenotypes related to Myopathy, Myofibrillar, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.17 ACTA1 APP CRYAB DMD FLNC LDB3

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. 8 71
21920752 2012
2
Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. 8 71
14681890 2003
3
A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. 8 71
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)]. 8 71
570292 1978
5
Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. 71
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. 71
25313375 2014
7
BAG3-related myofibrillar myopathy in a Chinese family. 71
21361913 2012
8
Infantile muscular dystrophy in Canadian aboriginals is an αB-crystallinopathy. 71
21337604 2011
9
Alpha B-crystallin mutation in dilated cardiomyopathy. 71
16483541 2006
10
Myofibrillar Myopathy 71
20301672 2005
11
Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant. 71
12812987 2003
12
Alteration of protein-protein interactions of congenital cataract crystallin mutants. 71
12601044 2003
13
Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy. 8
8792816 1996
14
Autosomal recessive, fatal infantile hypertonic muscular dystrophy among Canadian Natives. 71
8000975 1994
15
Mapping of additional markers in fission yeast, especially fus1 and three mfm genes. 38
8001176 1994
16
Analysis of the structural genes encoding M-factor in the fission yeast Schizosaccharomyces pombe: identification of a third gene, mfm3. 38
8196631 1994

Variations for Myopathy, Myofibrillar, 2

ClinVar genetic disease variations for Myopathy, Myofibrillar, 2:

6 (show all 19)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 CRYAB NM_001885.3(CRYAB): c.358A> G (p.Arg120Gly) single nucleotide variant Pathogenic rs104894201 11:111779658-111779658 11:111908934-111908934
2 CRYAB NM_001885.3(CRYAB): c.464_465del (p.Pro155fs) deletion Pathogenic 11:111779551-111779552 11:111908827-111908828
3 CRYAB NM_001885.3(CRYAB): c.451C> T (p.Gln151Ter) single nucleotide variant Pathogenic rs104894202 11:111779565-111779565 11:111908841-111908841
4 CRYAB NM_001885.3(CRYAB): c.60del (p.Ser21fs) deletion Pathogenic rs281865141 11:111782389-111782389 11:111911665-111911665
5 CRYAB NM_001885.3(CRYAB): c.325G> C (p.Asp109His) single nucleotide variant Pathogenic rs387907339 11:111779691-111779691 11:111908967-111908967
6 CRYAB NM_001885.3(CRYAB): c.343del (p.Ser115fs) deletion Pathogenic/Likely pathogenic rs281865142 11:111779673-111779673 11:111908949-111908949
7 CRYAB NM_001885.3(CRYAB): c.460G> A (p.Gly154Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs150516929 11:111779556-111779556 11:111908832-111908832
8 CRYAB NM_001885.3(CRYAB): c.152C> T (p.Pro51Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs2234704 11:111782297-111782297 11:111911573-111911573
9 CRYAB NM_001885.3(CRYAB): c.116C> T (p.Pro39Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs149787233 11:111782333-111782333 11:111911609-111911609
10 CRYAB NM_001885.3(CRYAB): c.*107A> G single nucleotide variant Uncertain significance rs886047686 11:111779381-111779381 11:111908657-111908657
11 CRYAB NM_001885.3(CRYAB): c.*39T> C single nucleotide variant Uncertain significance rs782808506 11:111779449-111779449 11:111908725-111908725
12 CRYAB NM_001885.3(CRYAB): c.102G> T (p.Glu34Asp) single nucleotide variant Uncertain significance rs886047688 11:111782347-111782347 11:111911623-111911623
13 CRYAB NM_001885.3(CRYAB): c.375A> C (p.Pro125=) single nucleotide variant Uncertain significance rs886047687 11:111779641-111779641 11:111908917-111908917
14 CRYAB NM_001885.3(CRYAB): c.*38G> C single nucleotide variant Uncertain significance rs781853968 11:111779450-111779450 11:111908726-111908726
15 CRYAB NM_001885.3(CRYAB): c.115C> G (p.Pro39Ala) single nucleotide variant Uncertain significance 11:111782334-111782334 11:111911610-111911610
16 CRYAB NM_001885.3(CRYAB): c.-21C> T single nucleotide variant Benign/Likely benign rs376222434 11:111782469-111782469 11:111911745-111911745
17 CRYAB NM_001885.3(CRYAB): c.165G> A (p.Leu55=) single nucleotide variant Benign rs2228387 11:111782284-111782284 11:111911560-111911560
18 CRYAB NM_001885.3(CRYAB): c.324+4T> G single nucleotide variant Benign rs11603779 11:111781047-111781047 11:111910323-111910323
19 CRYAB NM_001885.3(CRYAB): c.60C> T (p.Pro20=) single nucleotide variant Benign rs4252582 11:111782389-111782389 11:111911665-111911665

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

74
# 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 14)
# Name GO ID Score Top Affiliating Genes
1 perinuclear region of cytoplasm GO:0048471 9.83 PLEC LDB3 GSN DMD APP
2 focal adhesion GO:0005925 9.8 SYNPO2 PLEC GSN FLNC
3 axon GO:0030424 9.78 MYOT DMD CRYAB APP
4 cytoskeleton GO:0005856 9.76 SYNPO2 PLEC MYOT LDB3 GSN FLNC
5 actin cytoskeleton GO:0015629 9.71 SYNPO2 MYOT GSN ACTA1
6 lamellipodium GO:0030027 9.7 GSN DMD ACTA1
7 sarcolemma GO:0042383 9.62 PLEC MYOT FLNC DMD
8 intermediate filament cytoskeleton GO:0045111 9.54 PLEC NES
9 contractile fiber GO:0043292 9.51 PLEC CRYAB
10 astrocyte projection GO:0097449 9.46 DMD APP
11 costamere GO:0043034 9.43 PLEC FLNC DMD
12 sarcoplasm GO:0016528 9.13 PLEC GSN FLNC
13 Z disc GO:0030018 9.1 SYNPO2 MYOT LDB3 FLNC DMD CRYAB
14 cytoplasm GO:0005737 10.11 SYNPO2 PLEC NES MYOT LDB3 GSN

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

# Name GO ID Score Top Affiliating Genes
1 aging GO:0007568 9.43 GSN DMD CRYAB
2 synapse organization GO:0050808 9.37 MYOT APP
3 muscle contraction GO:0006936 9.33 MYOT CRYAB ACTA1
4 muscle filament sliding GO:0030049 9.32 DMD ACTA1
5 muscle fiber development GO:0048747 8.96 FLNC DMD
6 amyloid fibril formation GO:1990000 8.62 GSN APP

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

# Name GO ID Score Top Affiliating Genes
1 myosin binding GO:0017022 9.43 DMD ACTA1
2 structural constituent of cytoskeleton GO:0005200 9.43 PLEC DMD ACTA1
3 ankyrin binding GO:0030506 9.4 PLEC FLNC
4 alpha-actinin binding GO:0051393 9.37 SYNPO2 MYOT
5 actin binding GO:0003779 9.35 SYNPO2 PLEC MYOT GSN DMD
6 structural constituent of muscle GO:0008307 9.33 PLEC MYOT DMD
7 muscle alpha-actinin binding GO:0051371 9.32 SYNPO2 LDB3
8 cytoskeletal protein binding GO:0008092 8.92 PLEC LDB3 FLNC CRYAB
9 protein binding GO:0005515 10.2 SYNPO2 PLEC MYOT LDB3 GZMM GSN

Sources for Myopathy, Myofibrillar, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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