MCID: MSC115
MIFTS: 40

Muscular Dystrophy, Limb-Girdle, Type 1a

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

Aliases & Classifications for Muscular Dystrophy, Limb-Girdle, Type 1a

MalaCards integrated aliases for Muscular Dystrophy, Limb-Girdle, Type 1a:

Name: Muscular Dystrophy, Limb-Girdle, Type 1a 57 13 73
Lgmd1a 57 12 53 59 75 55
Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 1a 12 59 15
Limb-Girdle Muscular Dystrophy Due to Myotilin Deficiency 12 59
Limb-Girdle Muscular Dystrophy, Type 1a 29 6
Muscular Dystrophy, Proximal, Type 1a 57 53
Lgmd1 57 53
Muscular Dystrophy Limb-Girdle Type 1a 12
Limb-Girdle Muscular Dystrophy Type 1a 53
Proximal Muscular Dystrophy Type 1a 12
Muscular Dystrophy Proximal Type 1a 75
Limb-Girdle Muscular Dystrophy 1a 75

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant limb-girdle muscular dystrophy type 1a
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult,Elderly; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
genetic heterogeneity
slow progression
adult onset (mean 27 years)
variable clinical phenotype
hip girdle involvement precedes and is usually greater than shoulder girdle involvement
myotilinopathy is an allelic disorder with overlapping clinical features


HPO:

32
muscular dystrophy, limb-girdle, type 1a:
Onset and clinical course adult onset slow progression
Inheritance heterogeneous autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 159000
Disease Ontology 12 DOID:0110300
ICD10 33 G71.0
Orphanet 59 ORPHA266
UMLS via Orphanet 74 C1834659
ICD10 via Orphanet 34 G71.0
MedGen 42 C1834659
MeSH 44 D049288
UMLS 73 C1834659

Summaries for Muscular Dystrophy, Limb-Girdle, Type 1a

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 266Disease definitionAutosomal dominant limb-girdle muscular dystrophy type 1A (LGMD1A) is a subtype of autosomal dominant limb girdle muscular dystrophy characterized by an adult onset of proximal shoulder and hip girdle weakness (that later progresses to include distal weakness), nasal speech and dysarthria. Other frequent findings include tightened heel cords, reduced deep-tendon reflexes and elevated creatine kinase serum levels. Respiratory failure, as well as mild facial weakness and dysphagia, may also be observed.Visit the Orphanet disease page for more resources.

MalaCards based summary : Muscular Dystrophy, Limb-Girdle, Type 1a, also known as lgmd1a, is related to muscular dystrophy, limb-girdle, type 1f and muscular dystrophy, limb-girdle, type 1e. An important gene associated with Muscular Dystrophy, Limb-Girdle, Type 1a is MYOT (Myotilin), and among its related pathways/superpathways is Focal Adhesion. Affiliated tissues include skeletal muscle, and related phenotypes are shoulder girdle muscle weakness and proximal muscle weakness

OMIM : 57 LGMD1 is an autosomal dominant disorder characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region. Distal muscle weakness may occur later. Daniele et al. (2007) provided a review of therapeutic strategies in various forms of LGMD, including ongoing studies in gene therapy. (159000)

UniProtKB/Swiss-Prot : 75 Limb-girdle muscular dystrophy 1A: An autosomal dominant degenerative myopathy with onset within a mean age of 28 years. Characterized by progressive skeletal muscle weakness of the hip and shoulder girdles, later progressing to include distal weakness, as well as a distinctive dysarthric pattern of speech. Affected muscle exhibits disorganization and streaming of the Z-line.

Disease Ontology : 12 An autosomal dominant limb-girdle muscular dystrophy that has material basis in heterozygous mutation in the gene encoding myotilin (MYOT1) on chromosome 5q31.

Related Diseases for Muscular Dystrophy, Limb-Girdle, Type 1a

Diseases in the Limb-Girdle Muscular Dystrophy family:

Muscular Dystrophy, Limb-Girdle, Type 1a Muscular Dystrophy, Limb-Girdle, Type 1b
Muscular Dystrophy, Limb-Girdle, Type 2a Muscular Dystrophy, Limb-Girdle, Type 2b
Muscular Dystrophy, Limb-Girdle, Type 2c Muscular Dystrophy, Limb-Girdle, Type 2h
Muscular Dystrophy, Limb-Girdle, Type 2f Muscular Dystrophy, Limb-Girdle, Type 2g
Muscular Dystrophy, Limb-Girdle, Type 1e Muscular Dystrophy, Limb-Girdle, Type 1c
Muscular Dystrophy, Limb-Girdle, Type 2d Muscular Dystrophy, Limb-Girdle, Type 1f
Muscular Dystrophy, Limb-Girdle, Type 2j Limb-Girdle Muscular Dystrophy, Type 1g
Muscular Dystrophy, Limb-Girdle, Type 2l Muscular Dystrophy, Limb-Girdle, Type 1h
Muscular Dystrophy, Limb-Girdle, Type 2q Muscular Dystrophy, Limb-Girdle, Type 2r
Muscular Dystrophy, Limb-Girdle, Type 2x Muscular Dystrophy, Limb-Girdle, Type 2w
Muscular Dystrophy, Limb-Girdle, Type 2z Autosomal Dominant Limb-Girdle Muscular Dystrophy
Autosomal Recessive Limb-Girdle Muscular Dystrophy Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2b
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2e Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2f
Autosomal Recessive Limb-Girdle Muscular Dystrophy Type 2h Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 1c
Autosomal Dominant Limb-Girdle Muscular Dystrophy Type 1g

Diseases related to Muscular Dystrophy, Limb-Girdle, Type 1a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
# Related Disease Score Top Affiliating Genes
1 muscular dystrophy, limb-girdle, type 1f 31.5 CAV3 MYOT
2 muscular dystrophy, limb-girdle, type 1e 30.2 CAV3 FKRP MYOT
3 limb-girdle muscular dystrophy 26.3 CAPN3 CAV3 FKRP FLNC MYOT TRIM32
4 muscular dystrophy 26.3 CAPN3 CAV3 FKRP FLNC MYOT TRIM32
5 myopathy 25.9 CAPN3 CAV3 FKRP FLNC MYOT TRIM32
6 limb-girdle muscular dystrophy, type 1g 10.9
7 muscular dystrophy, limb-girdle, type 1h 10.9
8 myopathy, myofibrillar, 3 10.1 FLNC MYOT
9 myopathy, myofibrillar, 2 10.0 FLNC MYOT
10 myopathy, spheroid body 10.0 FLNC MYOT
11 myofibrillar myopathy 9.9 FLNC MYOT
12 leukemia, acute myeloid 9.9
13 leukemia 9.9
14 myeloid leukemia 9.9
15 autosomal recessive limb-girdle muscular dystrophy type 2b 9.8 CAPN3 CAV3
16 autosomal dominant limb-girdle muscular dystrophy 9.6 CAV3 FLNC MYOT
17 muscular dystrophy, limb-girdle, type 1c 9.6 CAV3 FKRP
18 polyglucosan body myopathy 1 with or without immunodeficiency 9.5 CAPN3 FKRP
19 muscular dystrophy, limb-girdle, type 2d 9.4 CAPN3 FKRP
20 distal muscular dystrophy 9.4 CAPN3 CAV3 MYOT
21 autosomal dominant limb-girdle muscular dystrophy type 1c 9.3 CAV3 FKRP MYOT
22 muscular dystrophy-dystroglycanopathy , type b, 5 9.2 CAV3 FKRP
23 muscular dystrophy, limb-girdle, type 2j 9.1 CAPN3 FKRP MYOT
24 atrial standstill 1 9.1 FKRP MYOT
25 isolated hyperckemia 9.0 CAPN3 CAV3 FKRP
26 muscular dystrophy, limb-girdle, type 2h 9.0 CAPN3 FKRP TRIM32
27 muscular dystrophy, limb-girdle, type 2f 9.0 CAPN3 FKRP TRIM32
28 muscular dystrophy-dystroglycanopathy , type c, 5 9.0 CAPN3 FKRP TRIM32
29 autosomal recessive limb-girdle muscular dystrophy 8.9 CAPN3 FKRP TRIM32
30 autosomal recessive limb-girdle muscular dystrophy type 2h 8.6 CAPN3 FKRP MYOT TRIM32
31 muscular dystrophy, limb-girdle, type 2g 8.6 CAPN3 FKRP MYOT TRIM32
32 muscle tissue disease 8.5 CAPN3 CAV3 FKRP MYOT
33 muscular dystrophy, limb-girdle, type 2b 8.0 CAPN3 CAV3 FKRP MYOT TRIM32

Graphical network of the top 20 diseases related to Muscular Dystrophy, Limb-Girdle, Type 1a:



Diseases related to Muscular Dystrophy, Limb-Girdle, Type 1a

Symptoms & Phenotypes for Muscular Dystrophy, Limb-Girdle, Type 1a

Symptoms via clinical synopsis from OMIM:

57
Muscle Soft Tissue:
dysarthria
hyporeflexia
shoulder girdle muscle weakness
emg shows myopathic changes
hip girdle muscle weakness
more
Skeletal Feet:
achilles tendon contractures

Voice:
nasal, dysarthic speech

Laboratory Abnormalities:
increased creatine kinase (ck)
increased ck-mb


Clinical features from OMIM:

159000

Human phenotypes related to Muscular Dystrophy, Limb-Girdle, Type 1a:

59 32 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 shoulder girdle muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0003547
2 proximal muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0003701
3 pelvic girdle muscle weakness 59 32 Very frequent (99-80%) HP:0003749
4 distal muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0002460
5 inability to walk 59 32 frequent (33%) Frequent (79-30%) HP:0002540
6 elevated serum creatine phosphokinase 59 32 frequent (33%) Frequent (79-30%) HP:0003236
7 difficulty climbing stairs 59 32 frequent (33%) Frequent (79-30%) HP:0003551
8 increased variability in muscle fiber diameter 59 32 frequent (33%) Frequent (79-30%) HP:0003557
9 difficulty standing 59 32 frequent (33%) Frequent (79-30%) HP:0003698
10 autophagic vacuoles 59 32 frequent (33%) Frequent (79-30%) HP:0003736
11 limited knee flexion/extension 59 32 frequent (33%) Frequent (79-30%) HP:0005085
12 limited elbow flexion 59 32 frequent (33%) Frequent (79-30%) HP:0006376
13 foot dorsiflexor weakness 59 32 frequent (33%) Frequent (79-30%) HP:0009027
14 hip flexor weakness 59 32 frequent (33%) Frequent (79-30%) HP:0012515
15 fatty replacement of skeletal muscle 59 32 frequent (33%) Frequent (79-30%) HP:0012548
16 increased endomysial connective tissue 59 32 frequent (33%) Frequent (79-30%) HP:0100297
17 facial hypotonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000297
18 dysphagia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002015
19 reduced vital capacity 59 32 occasional (7.5%) Occasional (29-5%) HP:0002792
20 respiratory failure 59 32 occasional (7.5%) Occasional (29-5%) HP:0002878
21 reduced maximal inspiratory pressure 59 32 occasional (7.5%) Occasional (29-5%) HP:0012496
22 emg: myopathic abnormalities 59 Frequent (79-30%)
23 respiratory insufficiency 59 Occasional (29-5%)
24 functional respiratory abnormality 59 Occasional (29-5%)
25 hyporeflexia 32 HP:0001265
26 achilles tendon contracture 32 HP:0001771
27 absent achilles reflex 32 HP:0003438
28 emg 32 frequent (33%) HP:0003458
29 muscle fiber splitting 32 HP:0003555
30 muscular dystrophy 32 HP:0003560
31 rimmed vacuoles 32 HP:0003805
32 late-onset distal muscle weakness 32 HP:0003810
33 nasal, dysarthic speech 32 HP:0008376

MGI Mouse Phenotypes related to Muscular Dystrophy, Limb-Girdle, Type 1a:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.02 CAPN3 CAV3 FKRP FLNC TRIM32

Drugs & Therapeutics for Muscular Dystrophy, Limb-Girdle, Type 1a

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Congenital Muscle Disease Study of Patient and Family Reported Medical Information Recruiting NCT01403402

Search NIH Clinical Center for Muscular Dystrophy, Limb-Girdle, Type 1a

Genetic Tests for Muscular Dystrophy, Limb-Girdle, Type 1a

Genetic tests related to Muscular Dystrophy, Limb-Girdle, Type 1a:

# Genetic test Affiliating Genes
1 Limb-Girdle Muscular Dystrophy, Type 1a 29 MYOT

Anatomical Context for Muscular Dystrophy, Limb-Girdle, Type 1a

MalaCards organs/tissues related to Muscular Dystrophy, Limb-Girdle, Type 1a:

41
Skeletal Muscle

Publications for Muscular Dystrophy, Limb-Girdle, Type 1a

Articles related to Muscular Dystrophy, Limb-Girdle, Type 1a:

# Title Authors Year
1
Developmental expression of myotilin, a gene mutated in limb-girdle muscular dystrophy type 1A. ( 11335118 )
2001
2
Use of a CEPH meiotic breakpoint panel to refine the locus of limb-girdle muscular dystrophy type 1A (LGMD1A) to a 2-Mb interval on 5q31. ( 9828127 )
1998
3
Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A. ( 8533815 )
1995

Variations for Muscular Dystrophy, Limb-Girdle, Type 1a

UniProtKB/Swiss-Prot genetic disease variations for Muscular Dystrophy, Limb-Girdle, Type 1a:

75
# Symbol AA change Variation ID SNP ID
1 MYOT p.Ser55Phe VAR_021569
2 MYOT p.Thr57Ile VAR_021570 rs28937597

ClinVar genetic disease variations for Muscular Dystrophy, Limb-Girdle, Type 1a:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 MYOT NM_006790.2(MYOT): c.170C> T (p.Thr57Ile) single nucleotide variant Pathogenic rs28937597 GRCh37 Chromosome 5, 137206510: 137206510
2 MYOT NM_006790.2(MYOT): c.170C> T (p.Thr57Ile) single nucleotide variant Pathogenic rs28937597 GRCh38 Chromosome 5, 137870821: 137870821
3 MYOT NM_006790.2(MYOT): c.164C> T (p.Ser55Phe) single nucleotide variant Pathogenic/Likely pathogenic rs121908457 GRCh37 Chromosome 5, 137206504: 137206504
4 MYOT NM_006790.2(MYOT): c.164C> T (p.Ser55Phe) single nucleotide variant Pathogenic/Likely pathogenic rs121908457 GRCh38 Chromosome 5, 137870815: 137870815
5 MYOT NM_006790.2(MYOT): c.17G> A (p.Arg6His) single nucleotide variant Pathogenic rs387906882 GRCh37 Chromosome 5, 137206357: 137206357
6 MYOT NM_006790.2(MYOT): c.17G> A (p.Arg6His) single nucleotide variant Pathogenic rs387906882 GRCh38 Chromosome 5, 137870668: 137870668

Expression for Muscular Dystrophy, Limb-Girdle, Type 1a

Search GEO for disease gene expression data for Muscular Dystrophy, Limb-Girdle, Type 1a.

Pathways for Muscular Dystrophy, Limb-Girdle, Type 1a

Pathways related to Muscular Dystrophy, Limb-Girdle, Type 1a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.57 CAPN3 CAV3 FLNC

GO Terms for Muscular Dystrophy, Limb-Girdle, Type 1a

Cellular components related to Muscular Dystrophy, Limb-Girdle, Type 1a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 T-tubule GO:0030315 9.26 CAPN3 CAV3
2 Z disc GO:0030018 9.26 CAPN3 CAV3 FLNC MYOT
3 dystrophin-associated glycoprotein complex GO:0016010 9.16 CAV3 FKRP
4 sarcolemma GO:0042383 8.92 CAV3 FKRP FLNC MYOT

Biological processes related to Muscular Dystrophy, Limb-Girdle, Type 1a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.32 CAPN3 TRIM32
2 muscle contraction GO:0006936 9.26 CAV3 MYOT
3 muscle organ development GO:0007517 9.16 CAPN3 CAV3
4 positive regulation of proteolysis GO:0045862 8.96 CAPN3 TRIM32
5 muscle cell cellular homeostasis GO:0046716 8.8 CAPN3 CAV3 TRIM32

Molecular functions related to Muscular Dystrophy, Limb-Girdle, Type 1a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein-containing complex scaffold activity GO:0032947 8.96 CAPN3 CAV3
2 structural constituent of muscle GO:0008307 8.62 CAPN3 MYOT

Sources for Muscular Dystrophy, Limb-Girdle, Type 1a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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