NEM1
MCID: NML002
MIFTS: 44

Nemaline Myopathy 1 (NEM1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Nemaline Myopathy 1

MalaCards integrated aliases for Nemaline Myopathy 1:

Name: Nemaline Myopathy 1 57 12 75 29 6 15 73
Cap Myopathy 1 57 75 29 6 73
Nem1 57 12 75
Nemaline Myopathy 1, Autosomal Dominant or Recessive 57 12
Nemaline Myopathy 1 Autosomal Dominant or Recessive 75
Myopathy, Nemaline, Type 1 40
Nemaline Myopathy, Type 1 76
Cap Myopathy Tpm3-Related 75
Cap Myopathy 73
Cap Disease 75
Capm1 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
genetic heterogeneity (see )
onset in childhood (range infancy to 10 years)
variable clinical severity
autosomal recessive disorder tends to be more severe


HPO:

32
nemaline myopathy 1:
Inheritance heterogeneous autosomal recessive inheritance autosomal dominant inheritance
Onset and clinical course juvenile onset


Classifications:



Summaries for Nemaline Myopathy 1

UniProtKB/Swiss-Prot : 75 Cap myopathy 1: A rare congenital skeletal muscle disorder characterized by the presence of cap-like structures which are well demarcated and peripherally located under the sarcolemma and show abnormal accumulation of sarcomeric proteins. Clinical features are early onset of hypotonia and slowly progressive muscle weakness. Respiratory problems are common. Nemaline myopathy 1: A form of nemaline myopathy with autosomal dominant or recessive inheritance. Nemaline myopathies are disorders characterized by muscle weakness of varying onset and severity, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. Autosomal dominant NEM1 is characterized by a moderate phenotype with onset between birth and early second decade of life. Weakness is diffuse and symmetric with slow progression often with need for a wheelchair in adulthood. The autosomal recessive form has onset at birth with moderate to severe hypotonia and diffuse weakness. In the most severe cases, death can occur before 2 years. Less severe cases have delayed major motor milestones, and these patients may walk, but often need a wheelchair before 10 years.

MalaCards based summary : Nemaline Myopathy 1, also known as cap myopathy 1, is related to cap myopathy and nemaline myopathy 4. An important gene associated with Nemaline Myopathy 1 is TPM3 (Tropomyosin 3), and among its related pathways/superpathways are Cell Cycle, Mitotic and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). Affiliated tissues include skeletal muscle and bone, and related phenotypes are pectus excavatum and high palate

Disease Ontology : 12 A nemaline myopathy characterized by onset typically in early childhood of mildly delayed motor development, hypotonia, generalized muscle weakness, and weakness of the proximal limb muscles and neck muscles, resulting in difficulty running and easy fatigability that has material basis in heterozygous, homozygous, or compound heterozygous mutation in the TPM3 gene on chromosome 1q21.

OMIM : 57 Nemaline myopathy-1 is a disorder characterized by muscle weakness, usually beginning in early childhood. The severity and pattern of muscle weakness varies, but most affected individuals show mildly delayed motor development, hypotonia, generalized muscle weakness, and weakness of the proximal limb muscles and neck muscles, resulting in difficulty running and easy fatigability. Most patients have respiratory insufficiency due to muscle weakness. Other common features include myopathic facies, high-arched palate, and scoliosis. Histologic findings on skeletal muscle biopsy are variable, even in patients with the same mutation. Muscle fibers can contain nemaline rod inclusions, or so-called subsarcolemmal 'cap' structures, as well as show overall fiber-type disproportion. It has been suggested that unknown modifying factors confer a tendency to one or another pattern of inclusions on skeletal muscle biopsy in those with TPM3 mutations (summary by Waddell et al., 2010 and Malfatti et al., 2013). For a discussion of genetic heterogeneity of nemaline myopathy, see 161800. (609284)

Wikipedia : 76 Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, hereditary... more...

Related Diseases for Nemaline Myopathy 1

Symptoms & Phenotypes for Nemaline Myopathy 1

Symptoms via clinical synopsis from OMIM:

57
Abdomen Gastrointestinal:
dysphagia

Skeletal Spine:
scoliosis

Head And Neck Face:
narrow face
long face
facial diplegia

Head And Neck Neck:
neck muscle weakness

Skeletal:
joint contractures

Respiratory:
respiratory insufficiency
restricted vital capacity

Skeletal Feet:
pes cavus

Muscle Soft Tissue:
facial diplegia
muscle weakness, proximal
emg shows myopathic changes
muscle weakness, lower limb, distal
muscle atrophy, lower limb, distal
more
Head And Neck Mouth:
high-arched palate

Neurologic Central Nervous System:
delayed motor development due to muscle weakness


Clinical features from OMIM:

609284

Human phenotypes related to Nemaline Myopathy 1:

32 (show all 19)
# Description HPO Frequency HPO Source Accession
1 pectus excavatum 32 HP:0000767
2 high palate 32 HP:0000218
3 dysphagia 32 HP:0002015
4 respiratory insufficiency 32 HP:0002093
5 scoliosis 32 HP:0002650
6 flexion contracture 32 HP:0001371
7 generalized muscle weakness 32 HP:0003324
8 pes cavus 32 HP:0001761
9 motor delay 32 HP:0001270
10 nemaline bodies 32 HP:0003798
11 narrow face 32 HP:0000275
12 long face 32 HP:0000276
13 proximal muscle weakness 32 HP:0003701
14 facial diplegia 32 HP:0001349
15 neck muscle weakness 32 HP:0000467
16 distal lower limb muscle weakness 32 HP:0009053
17 distal lower limb amyotrophy 32 HP:0008944
18 shoulder girdle muscle atrophy 32 HP:0003724
19 emg 32 HP:0003458

Drugs & Therapeutics for Nemaline Myopathy 1

Search Clinical Trials , NIH Clinical Center for Nemaline Myopathy 1

Genetic Tests for Nemaline Myopathy 1

Genetic tests related to Nemaline Myopathy 1:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 1 29 TPM3
2 Cap Myopathy 1 29

Anatomical Context for Nemaline Myopathy 1

MalaCards organs/tissues related to Nemaline Myopathy 1:

41
Skeletal Muscle, Bone

Publications for Nemaline Myopathy 1

Articles related to Nemaline Myopathy 1:

# Title Authors Year
1
Recessive MYPN mutations cause cap myopathy with occasional nemaline rods. ( 28220527 )
2017
2
The role of ultrasound in fetal congenital myopathy detection: a novel case of fetal-onset cap myopathy. ( 23804214 )
2013
3
Novel TPM3 mutation in a family with cap myopathy and review of the literature. ( 24239060 )
2013
4
Abnormal actin binding of aberrant I^-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy. ( 22084935 )
2012
5
Evidence for a dominant negative disease mechanism in cap myopathy due to TPM3. ( 20554445 )
2010
6
Cap myopathy caused by a mutation of the skeletal alpha-actin gene ACTA1. ( 20303757 )
2010
7
A TPM3 mutation causing cap myopathy. ( 19553118 )
2009

Variations for Nemaline Myopathy 1

UniProtKB/Swiss-Prot genetic disease variations for Nemaline Myopathy 1:

75
# Symbol AA change Variation ID SNP ID
1 TPM3 p.Met9Arg VAR_013460 rs80358247
2 TPM3 p.Arg168Cys VAR_070067 rs121964854
3 TPM3 p.Arg168His VAR_070069 rs121964852
4 TPM3 p.Ser88Phe VAR_071500
5 TPM3 p.Leu149Ile VAR_071504
6 TPM3 p.Glu151Ala VAR_071505
7 TPM3 p.Arg245Ile VAR_071508 rs797046047

ClinVar genetic disease variations for Nemaline Myopathy 1:

6 (show all 46)
# Gene Variation Type Significance SNP ID Assembly Location
1 TPM3 NM_152263.3(TPM3): c.26T> G (p.Met9Arg) single nucleotide variant Pathogenic rs80358247 GRCh37 Chromosome 1, 154164469: 154164469
2 TPM3 NM_152263.3(TPM3): c.26T> G (p.Met9Arg) single nucleotide variant Pathogenic rs80358247 GRCh38 Chromosome 1, 154191993: 154191993
3 TPM3 NM_152263.3(TPM3): c.857A> C (p.Ter286Ser) single nucleotide variant Uncertain significance rs199474720 GRCh37 Chromosome 1, 154140414: 154140414
4 TPM3 NM_152263.3(TPM3): c.857A> C (p.Ter286Ser) single nucleotide variant Uncertain significance rs199474720 GRCh38 Chromosome 1, 154167938: 154167938
5 TPM3 NM_152263.3(TPM3): c.855-1G> A single nucleotide variant Uncertain significance rs113605263 GRCh37 Chromosome 1, 154140417: 154140417
6 TPM3 NM_152263.3(TPM3): c.855-1G> A single nucleotide variant Uncertain significance rs113605263 GRCh38 Chromosome 1, 154167941: 154167941
7 TPM3 NM_152263.3(TPM3): c.94C> T (p.Gln32Ter) single nucleotide variant Pathogenic rs80358248 GRCh37 Chromosome 1, 154164401: 154164401
8 TPM3 NM_152263.3(TPM3): c.94C> T (p.Gln32Ter) single nucleotide variant Pathogenic rs80358248 GRCh38 Chromosome 1, 154191925: 154191925
9 TPM3 NM_152263.3(TPM3): c.503G> A (p.Arg168His) single nucleotide variant Pathogenic rs121964852 GRCh37 Chromosome 1, 154145447: 154145447
10 TPM3 NM_152263.3(TPM3): c.503G> A (p.Arg168His) single nucleotide variant Pathogenic rs121964852 GRCh38 Chromosome 1, 154172971: 154172971
11 TPM3 NM_152263.3(TPM3): c.855delA (p.Ter286Asnfs) deletion Pathogenic rs199474719 GRCh37 Chromosome 1, 154140416: 154140416
12 TPM3 NM_152263.3(TPM3): c.855delA (p.Ter286Asnfs) deletion Pathogenic rs199474719 GRCh38 Chromosome 1, 154167940: 154167940
13 TPM3 NM_152263.3(TPM3): c.502C> G (p.Arg168Gly) single nucleotide variant Pathogenic/Likely pathogenic rs121964854 GRCh37 Chromosome 1, 154145448: 154145448
14 TPM3 NM_152263.3(TPM3): c.502C> G (p.Arg168Gly) single nucleotide variant Pathogenic/Likely pathogenic rs121964854 GRCh38 Chromosome 1, 154172972: 154172972
15 TPM3 NM_152263.3(TPM3): c.502C> T (p.Arg168Cys) single nucleotide variant Pathogenic rs121964854 GRCh37 Chromosome 1, 154145448: 154145448
16 TPM3 NM_152263.3(TPM3): c.502C> T (p.Arg168Cys) single nucleotide variant Pathogenic rs121964854 GRCh38 Chromosome 1, 154172972: 154172972
17 TPM3 NM_152263.3(TPM3): c.92A> C (p.Lys31Thr) single nucleotide variant Benign/Likely benign rs62000429 GRCh37 Chromosome 1, 154164403: 154164403
18 TPM3 NM_152263.3(TPM3): c.92A> C (p.Lys31Thr) single nucleotide variant Benign/Likely benign rs62000429 GRCh38 Chromosome 1, 154191927: 154191927
19 TPM3 NM_152263.3(TPM3): c.673_675delGAA (p.Glu225del) deletion Pathogenic rs876661406 GRCh37 Chromosome 1, 154143155: 154143157
20 TPM3 NM_152263.3(TPM3): c.673_675delGAA (p.Glu225del) deletion Pathogenic rs876661406 GRCh38 Chromosome 1, 154170679: 154170681
21 TPM3 NM_152263.3(TPM3): c.657_659delAGA (p.Glu219del) deletion Pathogenic rs876661407 GRCh37 Chromosome 1, 154143171: 154143173
22 TPM3 NM_152263.3(TPM3): c.657_659delAGA (p.Glu219del) deletion Pathogenic rs876661407 GRCh38 Chromosome 1, 154170695: 154170697
23 TPM3 NM_152263.3(TPM3): c.788C> G (p.Ala263Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 154141847: 154141847
24 TPM3 NM_152263.3(TPM3): c.788C> G (p.Ala263Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 154169371: 154169371
25 TPM3 NM_152263.3(TPM3): c.65G> A (p.Arg22Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 154191954: 154191954
26 TPM3 NM_152263.3(TPM3): c.65G> A (p.Arg22Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 154164430: 154164430
27 TPM3 NM_152263.3(TPM3): c.758C> A (p.Thr253Lys) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 154142893: 154142893
28 TPM3 NM_152263.3(TPM3): c.758C> A (p.Thr253Lys) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 154170417: 154170417
29 TPM3 NM_152263.3(TPM3): c.760A> G (p.Ile254Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 154142891: 154142891
30 TPM3 NM_152263.3(TPM3): c.760A> G (p.Ile254Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 154170415: 154170415
31 TPM3 NM_152263.3(TPM3): c.144G> A (p.Gln48=) single nucleotide variant Likely benign rs765923858 GRCh38 Chromosome 1, 154191285: 154191285
32 TPM3 NM_152263.3(TPM3): c.144G> A (p.Gln48=) single nucleotide variant Likely benign rs765923858 GRCh37 Chromosome 1, 154163761: 154163761
33 TPM3 NM_152263.3(TPM3): c.737C> T (p.Ser246Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 154142914: 154142914
34 TPM3 NM_152263.3(TPM3): c.737C> T (p.Ser246Leu) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 154170438: 154170438
35 TPM3 NM_152263.3(TPM3): c.706-9T> A single nucleotide variant Likely benign rs931328025 GRCh37 Chromosome 1, 154142954: 154142954
36 TPM3 NM_152263.3(TPM3): c.706-9T> A single nucleotide variant Likely benign rs931328025 GRCh38 Chromosome 1, 154170478: 154170478
37 TPM3 NM_152263.3(TPM3): c.483G> A (p.Arg161=) single nucleotide variant Likely benign rs150586027 GRCh37 Chromosome 1, 154145572: 154145572
38 TPM3 NM_152263.3(TPM3): c.483G> A (p.Arg161=) single nucleotide variant Likely benign rs150586027 GRCh38 Chromosome 1, 154173096: 154173096
39 TPM3 NM_152263.3(TPM3): c.298C> G (p.Leu100Val) single nucleotide variant Likely pathogenic rs121964853 GRCh37 Chromosome 1, 154148670: 154148670
40 TPM3 NM_152263.3(TPM3): c.298C> G (p.Leu100Val) single nucleotide variant Likely pathogenic rs121964853 GRCh38 Chromosome 1, 154176194: 154176194
41 TPM3 NM_152263.3(TPM3): c.262T> C (p.Ser88Pro) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 154148706: 154148706
42 TPM3 NM_152263.3(TPM3): c.262T> C (p.Ser88Pro) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 154176230: 154176230
43 TPM3 NC_000001.11: g.(?_154191166)_(154192038_?)del deletion Uncertain significance GRCh37 Chromosome 1, 154163642: 154164514
44 TPM3 NC_000001.11: g.(?_154191166)_(154192038_?)del deletion Uncertain significance GRCh38 Chromosome 1, 154191166: 154192038
45 TPM3 NM_152263.3(TPM3): c.567-4A> C single nucleotide variant Uncertain significance rs199517163 GRCh37 Chromosome 1, 154143968: 154143968
46 TPM3 NM_152263.3(TPM3): c.567-4A> C single nucleotide variant Uncertain significance rs199517163 GRCh38 Chromosome 1, 154171492: 154171492

Expression for Nemaline Myopathy 1

Search GEO for disease gene expression data for Nemaline Myopathy 1.

Pathways for Nemaline Myopathy 1

Pathways related to Nemaline Myopathy 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.78 LPIN1 LPIN3 NUP107 RANGAP1
2
Show member pathways
12.32 ALAS1 LPIN1 LPIN3
3
Show member pathways
12.28 LPIN1 LPIN3 NUP107 RANGAP1
4
Show member pathways
11.96 LPIN1 LPIN3 NUP107
5
Show member pathways
11.72 LPIN1 LPIN3
6 11.67 NUP107 RANGAP1
7 11.52 LPIN1 LPIN3
8 11.04 LPIN1 LPIN3
9 10.07 LPIN1 LPIN3

GO Terms for Nemaline Myopathy 1

Cellular components related to Nemaline Myopathy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 kinetochore GO:0000776 9.32 NUP107 RANGAP1
2 condensed chromosome kinetochore GO:0000777 9.26 NUP107 RANGAP1
3 nuclear pore GO:0005643 9.16 NUP107 RANGAP1
4 nuclear membrane GO:0031965 9.13 LPIN1 NUP107 RANGAP1
5 nuclear envelope GO:0005635 8.8 LPIN1 NUP107 RANGAP1

Biological processes related to Nemaline Myopathy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 dephosphorylation GO:0016311 9.4 LPIN1 LPIN3
2 fatty acid metabolic process GO:0006631 9.37 LPIN1 LPIN3
3 cellular response to insulin stimulus GO:0032869 9.32 LPIN1 LPIN3
4 phosphatidylcholine biosynthetic process GO:0006656 9.26 LPIN1 LPIN3
5 triglyceride biosynthetic process GO:0019432 9.16 LPIN1 LPIN3
6 fatty acid catabolic process GO:0009062 8.96 LPIN1 LPIN3
7 phosphatidylethanolamine biosynthetic process GO:0006646 8.62 LPIN1 LPIN3

Molecular functions related to Nemaline Myopathy 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidate phosphatase activity GO:0008195 8.62 LPIN1 LPIN3

Sources for Nemaline Myopathy 1

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