LGMDR8
MCID: MSC172
MIFTS: 42

Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8 (LGMDR8)

Categories: Genetic diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

MalaCards integrated aliases for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

Name: Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8 57 74
Sarcotubular Myopathy 57 53 59 74 29 6
Lgmd2h 57 53 59 74 55
Muscular Dystrophy, Limb-Girdle, Type 2h 57 74 13
Muscular Dystrophy Hutterite Type 53 74
Lgmdr8 57 74
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2h 59
Limb-Girdle Muscular Dystrophy Due to Trim32 Deficiency 59
Muscular Dystrophy, Limb-Girdle, Type 2h; Lgmd2h 57
Dystrophy, Muscular, Limb-Girdle, Type 2h 40
Limb-Girdle Muscular Dystrophy Type 2h 53
Muscular Dystrophy Limb-Girdle Type 2h 53
Muscular Dystrophy, Hutterite Type 57
Limb-Girdle Muscular Dystrophy 2h 74

Characteristics:

Orphanet epidemiological data:

59
autosomal recessive limb-girdle muscular dystrophy type 2h
Inheritance: Autosomal recessive; Age of onset: Adolescent,Adult,Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
highly variable phenotype and severity
onset usually in childhood (1 to 9 years of age)
high frequency in hutterite population


HPO:

32
muscular dystrophy, limb-girdle, autosomal recessive 8:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

MeSH 44 D049288
ICD10 via Orphanet 34 G71.0
UMLS via Orphanet 73 C0270968
Orphanet 59 ORPHA1878
MedGen 42 C0270968

Summaries for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1878DefinitionA mild subtype of autosomal recessive limb girdle muscular dystrophy characterized by slowly progressive proximal muscle weakness and wasting of the pelvic and shoulder girdles with onset that usually occurs during the second or third decade of life. Clinical presentation is variable and can include calf psuedohypertrophy, joint contractures, scapular winging, muscle cramping and/or facial and respiratory muscle involvement.Visit the Orphanet disease page for more resources.

MalaCards based summary : Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8, also known as sarcotubular myopathy, is related to autosomal recessive limb-girdle muscular dystrophy type 2h and myofibrillar myopathy, and has symptoms including waddling gait, exercise-induced myalgia and quadriceps muscle weakness. An important gene associated with Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8 is TRIM32 (Tripartite Motif Containing 32), and among its related pathways/superpathways are Cardiac conduction and Striated Muscle Contraction. Affiliated tissues include skeletal muscle, and related phenotypes are waddling gait and increased variability in muscle fiber diameter

UniProtKB/Swiss-Prot : 74 Muscular dystrophy, limb-girdle, autosomal recessive 8: An autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life.

More information from OMIM: 254110 PS253600

Related Diseases for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Diseases in the Limb-Girdle Muscular Dystrophy family:

Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 1 Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 2
Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 5 Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8
Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 6 Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 7
Muscular Dystrophy, Limb-Girdle, Autosomal Dominant 1 Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 4
Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 3 Muscular Dystrophy, Limb-Girdle, Autosomal Dominant 2
Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 10 Muscular Dystrophy, Limb-Girdle, Autosomal Dominant 3
Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 12 Muscular Dystrophy, Limb-Girdle, Type 1h
Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 17 Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 18
Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 25 Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 21
Muscular Dystrophy, Limb-Girdle, Autosomal Dominant 4 Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 23
Autosomal Dominant Limb-Girdle Muscular Dystrophy Autosomal Recessive Limb-Girdle Muscular Dystrophy
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2a Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2b
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2c Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2d
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2f Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2g
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2h Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2j
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2l Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2q
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2w Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2x
Limb-Girdle Muscular Dystrophy Type 1a Limb-Girdle Muscular Dystrophy Type 1b
Limb-Girdle Muscular Dystrophy Type 1c

Diseases related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 autosomal recessive limb-girdle muscular dystrophy type 2h 32.1 TRIM32 FKRP CAPN3
2 myofibrillar myopathy 29.9 TTN TCAP
3 miyoshi muscular dystrophy 29.5 TTN DYSF CAPN3
4 myopathy 29.4 TTN DYSF CAPN3
5 muscular dystrophy 28.1 TTN TRIM32 TCAP FKRP DYSF CAPN3
6 limb-girdle muscular dystrophy 28.0 TTN TRIM32 TCAP FKRP DYSF CAPN3
7 muscular dystrophy-dystroglycanopathy , type c, 5 27.8 TTN TRIM32 TCAP FKRP DYSF CAPN3
8 reducing body myopathy 11.4
9 bardet-biedl syndrome 10.6
10 polydactyly 10.5
11 bardet-biedl syndrome 11 10.4
12 learning disability 10.4
13 paresthesia 10.1 FKRP CAPN3
14 polyglucosan body myopathy 1 with or without immunodeficiency 10.1 FKRP CAPN3
15 familial isolated dilated cardiomyopathy 10.0 TTN TCAP
16 tibial muscular dystrophy 10.0 TTN CAPN3
17 autosomal recessive limb-girdle muscular dystrophy type 2l 10.0 FKRP DYSF
18 autosomal recessive limb-girdle muscular dystrophy type 2f 9.9 DYSF CAPN3
19 autosomal recessive limb-girdle muscular dystrophy type 2c 9.9 DYSF CAPN3
20 autosomal recessive limb-girdle muscular dystrophy type 2b 9.8 DYSF CAPN3
21 dysferlinopathy 9.8 DYSF CAPN3
22 muscular dystrophy, congenital, lmna-related 9.8 TTN FKRP
23 rigid spine muscular dystrophy 1 9.8 TTN DYSF
24 isolated hyperckemia 9.8 TCAP FKRP CAPN3
25 bethlem myopathy 1 9.7 DYSF CAPN3
26 autosomal recessive limb-girdle muscular dystrophy type 2j 9.7 TTN FKRP CAPN3
27 autosomal recessive limb-girdle muscular dystrophy type 2g 9.6 TCAP DYSF CAPN3
28 autosomal recessive limb-girdle muscular dystrophy type 2d 9.5 FKRP DYSF CAPN3
29 atrial standstill 1 9.5 TTN FKRP
30 muscle tissue disease 9.5 FKRP DYSF CAPN3
31 myositis 9.5 TTN DYSF CAPN3
32 autosomal recessive limb-girdle muscular dystrophy type 2a 9.1 TTN FKRP DYSF CAPN3
33 autosomal recessive limb-girdle muscular dystrophy 8.8 TRIM32 TCAP FKRP DYSF CAPN3
34 muscular disease 8.7 TTN TRIM32 FKRP DYSF CAPN3
35 muscular dystrophy, limb-girdle, autosomal recessive 7 8.4 TTN TRIM32 TCAP FKRP DYSF CAPN3
36 muscular dystrophy, limb-girdle, autosomal recessive 6 8.4 TTN TRIM32 TCAP FKRP DYSF CAPN3
37 muscular dystrophy, limb-girdle, autosomal recessive 2 8.4 TTN TRIM32 TCAP FKRP DYSF CAPN3

Graphical network of the top 20 diseases related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:



Diseases related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Symptoms & Phenotypes for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Human phenotypes related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

59 32 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 waddling gait 59 32 Very frequent (99-80%) HP:0002515
2 increased variability in muscle fiber diameter 59 32 Very frequent (99-80%) HP:0003557
3 gait disturbance 59 Very frequent (99-80%)
4 facial palsy 32 HP:0010628
5 myopathy 59 Very frequent (99-80%)
6 elevated serum creatine phosphokinase 59 Very frequent (99-80%)
7 emg abnormality 59 Very frequent (99-80%)
8 areflexia 32 HP:0001284
9 emg: myopathic abnormalities 32 HP:0003458
10 proximal muscle weakness in lower limbs 59 Very frequent (99-80%)
11 mask-like facies 59 Very frequent (99-80%)
12 pelvic girdle muscle weakness 32 HP:0003749
13 hyporeflexia 32 HP:0001265
14 tall stature 59 Frequent (79-30%)
15 muscular dystrophy 32 HP:0003560
16 neck flexor weakness 32 HP:0003722
17 gowers sign 32 HP:0003391
18 centrally nucleated skeletal muscle fibers 32 HP:0003687
19 exercise-induced myalgia 32 HP:0003738
20 calf muscle pseudohypertrophy 32 HP:0003707
21 quadriceps muscle weakness 32 HP:0003731
22 shoulder girdle muscle weakness 32 HP:0003547
23 pelvic girdle muscle atrophy 32 HP:0008988
24 shoulder girdle muscle atrophy 32 HP:0003724
25 elevated serum creatine kinase 32 HP:0003236

Symptoms via clinical synopsis from OMIM:

57
Neurologic Peripheral Nervous System:
areflexia
hyporeflexia

Head And Neck Face:
facial muscle weakness
'flat smile'

Head And Neck Neck:
neck flexor muscle weakness

Muscle Soft Tissue:
waddling gait
pelvic girdle muscle weakness
calf muscle pseudohypertrophy
quadriceps muscle weakness
shoulder girdle muscle weakness
more
Laboratory Abnormalities:
increased serum creatine kinase

Clinical features from OMIM:

254110

UMLS symptoms related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:


waddling gait, exercise-induced myalgia, quadriceps muscle weakness, facial paresis

MGI Mouse Phenotypes related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 DYSF FKRP PRKN TCAP TRIM32 TTN
2 cardiovascular system MP:0005385 9.55 CAPN3 FKRP PRKN TCAP TTN
3 homeostasis/metabolism MP:0005376 9.5 CAPN3 DYSF FKRP PRKN TCAP TRIM32
4 muscle MP:0005369 9.17 CAPN3 DYSF FKRP PRKN TCAP TRIM32

Drugs & Therapeutics for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Search Clinical Trials , NIH Clinical Center for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Genetic Tests for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Genetic tests related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

# Genetic test Affiliating Genes
1 Sarcotubular Myopathy 29 TRIM32

Anatomical Context for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

MalaCards organs/tissues related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

41
Skeletal Muscle

Publications for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Articles related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

(show all 30)
# Title Authors PMID Year
1
Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H. 38 8 71
15786463 2005
2
Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. 9 8 71
11822024 2002
3
Phenotypic variability in two brothers with sarcotubular myopathy. 38 8 71
10399877 1999
4
Sarcotubular myopathy. A newly recognized, benign, congenital, familial muscle disease. 38 8 71
4269389 1973
5
A population-based study of autosomal-recessive disease-causing mutations in a founder population. 8 71
22981120 2012
6
Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. 8 71
17994549 2008
7
Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I. 8 71
15886712 2005
8
TRIM32 is an E3 ubiquitin ligase for dysbindin. 38 71
19349376 2009
9
Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component. 38 8
19155210 2009
10
The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations. 9 8
15580560 2005
11
229th ENMC international workshop: Limb girdle muscular dystrophies - Nomenclature and reformed classification Naarden, the Netherlands, 17-19 March 2017. 8
30055862 2018
12
Low prevalence of psychoses among the Hutterites, an isolated religious community. 8
10873912 2000
13
A gene for autosomal recessive limb-girdle muscular dystrophy in Manitoba Hutterites maps to chromosome region 9q31-q33: evidence for another limb-girdle muscular dystrophy locus. 8
9634523 1998
14
Limb girdle muscular dystrophy in Manitoba Hutterites does not map to any of the known LGMD loci. 8
9332671 1997
15
Muscular dystrophy in Saskatchewan Hutterites. 8
4061485 1985
16
History and relevance of the Hutterite population for genetic studies. 8
3904447 1985
17
Autosomal recessive muscular dystrophy in Manitoba Hutterites. 8
1248180 1976
18
Use of SNP array analysis to identify a novel TRIM32 mutation in limb-girdle muscular dystrophy type 2H. 9 38
19303295 2009
19
Novel TRIM32 mutation in sarcotubular myopathy. 38
31309175 2019
20
Scapuloperoneal muscular dystrophy phenotype due to TRIM32-sarcotubular myopathy in South Dakota Hutterite. 38
23142638 2013
21
The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype. 38
21775502 2011
22
Limb-girdle muscular dystrophy 2H and the role of TRIM32. 38
21496629 2011
23
Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H. 38
19492423 2009
24
The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb-girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB. 9
16816390 2006
25
Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin. 38
16243356 2005
26
[Limb girdle muscular dystrophies]. 9
15316618 2004
27
Molecular bases of autosomal recessive limb-girdle muscular dystrophies. 9
14959561 2003
28
Dysferlin protein analysis in limb-girdle muscular dystrophies. 9
11665864 2001
29
[Sarcotubular myopathy]. 38
11555976 2001
30
Seven autosomal recessive limb-girdle muscular dystrophies in the Brazilian population: from LGMD2A to LGMD2G. 9
10069710 1999

Variations for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

ClinVar genetic disease variations for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TRIM32 NM_012210.3(TRIM32): c.1459G> A (p.Asp487Asn) single nucleotide variant Pathogenic rs111033570 9:119461480-119461480 9:116699201-116699201
2 TRIM32 TRIM32, 1-BP DEL, 1559C deletion Pathogenic
3 TRIM32 NM_012210.3(TRIM32): c.1181G> A (p.Arg394His) single nucleotide variant Uncertain significance rs121434447 9:119461202-119461202 9:116698923-116698923
4 TRIM32 NM_012210.3(TRIM32): c.404C> T (p.Thr135Ile) single nucleotide variant Uncertain significance rs141953092 9:119460425-119460425 9:116698146-116698146
5 TRIM32 NM_012210.3(TRIM32): c.872T> G (p.Ile291Ser) single nucleotide variant Uncertain significance 9:119460893-119460893 9:116698614-116698614
6 TRIM32 NM_012210.3(TRIM32): c.1168C> T (p.Arg390Cys) single nucleotide variant Uncertain significance rs754554333 9:119461189-119461189 9:116698910-116698910

UniProtKB/Swiss-Prot genetic disease variations for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8:

74
# Symbol AA change Variation ID SNP ID
1 TRIM32 p.Asp487Asn VAR_018725 rs111033570
2 TRIM32 p.Arg394His VAR_042939 rs121434447

Expression for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Search GEO for disease gene expression data for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8.

Pathways for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

GO Terms for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

Cellular components related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.8 TTN TRIM32 TCAP PRKN FKRP CAPN3
2 sarcolemma GO:0042383 9.37 FKRP DYSF
3 sarcomere GO:0030017 9.26 TTN TCAP
4 T-tubule GO:0030315 9.16 DYSF CAPN3
5 I band GO:0031674 8.96 TTN TCAP
6 Z disc GO:0030018 8.8 TTN TCAP CAPN3

Biological processes related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8 according to GeneCards Suite gene sharing:

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 regulation of catalytic activity GO:0050790 9.59 TTN CAPN3
2 positive regulation of protein catabolic process GO:0045732 9.58 TRIM32 PRKN
3 fat cell differentiation GO:0045444 9.58 TRIM32 DYSF
4 response to calcium ion GO:0051592 9.57 TTN CAPN3
5 protein K48-linked ubiquitination GO:0070936 9.56 TRIM32 PRKN
6 cardiac muscle contraction GO:0060048 9.55 TTN TCAP
7 protein destabilization GO:0031648 9.54 PRKN CAPN3
8 muscle filament sliding GO:0030049 9.52 TTN TCAP
9 muscle cell cellular homeostasis GO:0046716 9.51 TRIM32 CAPN3
10 cardiac muscle tissue morphogenesis GO:0055008 9.49 TTN TCAP
11 positive regulation of proteolysis GO:0045862 9.48 TRIM32 CAPN3
12 cardiac myofibril assembly GO:0055003 9.46 TTN TCAP
13 cardiac muscle fiber development GO:0048739 9.43 TTN TCAP
14 skeletal muscle thin filament assembly GO:0030240 9.4 TTN TCAP
15 skeletal muscle myosin thick filament assembly GO:0030241 9.37 TTN TCAP
16 cardiac muscle hypertrophy GO:0003300 9.32 TTN TCAP
17 positive regulation of tumor necrosis factor-mediated signaling pathway GO:1903265 9.26 TRIM32 PRKN
18 detection of muscle stretch GO:0035995 9.16 TTN TCAP
19 sarcomerogenesis GO:0048769 8.96 TTN TCAP
20 sarcomere organization GO:0045214 8.8 TTN TCAP CAPN3

Molecular functions related to Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ubiquitin binding GO:0043130 9.26 TRIM32 PRKN
2 protein self-association GO:0043621 9.16 TTN TRIM32
3 titin binding GO:0031432 8.96 TCAP CAPN3
4 structural constituent of muscle GO:0008307 8.8 TTN TCAP CAPN3

Sources for Muscular Dystrophy, Limb-Girdle, Autosomal Recessive 8

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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