NEM2
MCID: NML003
MIFTS: 49

Nemaline Myopathy 2 (NEM2)

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

Aliases & Classifications for Nemaline Myopathy 2

MalaCards integrated aliases for Nemaline Myopathy 2:

Name: Nemaline Myopathy 2 58 12 76 30 6 15 74
Nemaline Myopathy 2, Autosomal Recessive 58 12 30 13 6
Nem2 58 12 76
Neb-Related Nemaline Myopathy 76
Myopathy, Nemaline, Type 2 41
Nemaline Myopathy, Type 2 77

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
extraocular muscles are not involved
highly variable severity, ranging from 'typical' to 'severe' disease
slowly progressive or nonprogressive course
many adults with typical form remain ambulatory
death at birth or within first 2 years of life (severe form)


HPO:

33
nemaline myopathy 2:
Onset and clinical course infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Nemaline Myopathy 2

OMIM : 58 Nemaline myopathy-2 is an autosomal recessive skeletal muscle disorder with a wide range of severity. The most common clinical presentation is early-onset (in infancy or childhood) muscle weakness predominantly affecting proximal limb muscles. Muscle biopsy shows accumulation of Z-disc and thin filament proteins into aggregates named 'nemaline bodies' or 'nemaline rods,' usually accompanied by disorganization of the muscle Z discs. The clinical and histologic spectrum of entities caused by variants in the NEB gene is a continuum, ranging in severity from the severe form with perinatal onset and fetal death to milder forms with later onset. The distribution of weakness can vary from generalized muscle weakness, more pronounced in proximal limb muscles, to distal-only involvement, although neck flexor weakness appears to be rather consistent. Histologic patterns range from a severe usually nondystrophic disturbance of the myofibrillar pattern to an almost normal pattern, with or without nemaline bodies, sometimes combined with cores (summary by Lehtokari et al., 2014). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800). Mutations in the NEB gene are the most common cause of nemaline myopathy (Lehtokari et al., 2006). (256030)

MalaCards based summary : Nemaline Myopathy 2, also known as nemaline myopathy 2, autosomal recessive, is related to intermediate congenital nemaline myopathy and childhood-onset nemaline myopathy, and has symptoms including generalized muscle weakness, waddling gait and facial paresis. An important gene associated with Nemaline Myopathy 2 is NEB (Nebulin), and among its related pathways/superpathways are Vascular smooth muscle contraction and Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways. Affiliated tissues include skeletal muscle, eye and bone, and related phenotypes are low-set ears and high palate

Disease Ontology : 12 A nemaline myopathy that has material basis in homozygous or compound heterozygous mutation in the NEB gene on chromosome 2q23.

UniProtKB/Swiss-Prot : 76 Nemaline myopathy 2: A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination.

Wikipedia : 77 Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, hereditary... more...

Related Diseases for Nemaline Myopathy 2

Graphical network of the top 20 diseases related to Nemaline Myopathy 2:



Diseases related to Nemaline Myopathy 2

Symptoms & Phenotypes for Nemaline Myopathy 2

Human phenotypes related to Nemaline Myopathy 2:

33 (show all 39)
# Description HPO Frequency HPO Source Accession
1 low-set ears 33 HP:0000369
2 high palate 33 HP:0000218
3 dysphagia 33 HP:0002015
4 scoliosis 33 HP:0002650
5 hyperlordosis 33 HP:0003307
6 facial palsy 33 HP:0010628
7 neonatal hypotonia 33 HP:0001319
8 flexion contracture 33 HP:0001371
9 abnormality of the eye 33 HP:0000478
10 respiratory insufficiency due to muscle weakness 33 HP:0002747
11 generalized muscle weakness 33 HP:0003324
12 cleft palate 33 HP:0000175
13 long philtrum 33 HP:0000343
14 feeding difficulties 33 HP:0011968
15 inability to walk 33 HP:0002540
16 waddling gait 33 HP:0002515
17 spinal rigidity 33 HP:0003306
18 emg: myopathic abnormalities 33 HP:0003458
19 apnea 33 HP:0002104
20 arthrogryposis multiplex congenita 33 HP:0002804
21 motor delay 33 HP:0001270
22 type 1 muscle fiber predominance 33 HP:0003803
23 nemaline bodies 33 HP:0003798
24 slender build 33 HP:0001533
25 polyhydramnios 33 HP:0001561
26 areflexia 33 HP:0001284
27 hyporeflexia 33 HP:0001265
28 proximal muscle weakness 33 HP:0003701
29 decreased fetal movement 33 HP:0001558
30 myopathic facies 33 HP:0002058
31 neck flexor weakness 33 HP:0003722
32 limb muscle weakness 33 HP:0003690
33 frequent falls 33 HP:0002359
34 bulbar palsy 33 HP:0001283
35 emg: neuropathic changes 33 HP:0003445
36 abnormality of the rib cage 33 HP:0001547
37 mildly elevated creatine kinase 33 HP:0008180
38 late-onset distal muscle weakness 33 HP:0003810
39 mitochondrial depletion 33 HP:0030059

Symptoms via clinical synopsis from OMIM:

58
Abdomen Gastrointestinal:
dysphagia
poor feeding

Respiratory:
respiratory insufficiency due to muscle weakness
absence of spontaneous respiration (severe form)

Neurologic Central Nervous System:
areflexia
hyporeflexia
delayed motor development
absent gag reflex
slow gross motor activity
more
Head And Neck Mouth:
high-arched palate
cleft palate (severe form)

Head And Neck Neck:
neck flexor muscle weakness

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (severe form)
fetal hydrops (severe form)

Chest External Features:
chest deformities

Head And Neck Eyes:
hypertelorism (severe form)

Skeletal Feet:
talipes (severe form)

Skeletal Spine:
hyperlordosis
scoliosis (onset around puberty)
rigid spine

Muscle Soft Tissue:
type 1 muscle fiber predominance
neck muscle weakness
frequent falls
facial muscle weakness
distal limb muscle weakness occurs later
more
Head And Neck Face:
myopathic facies
facial muscle weakness
long philtrum (severe form)

Skeletal:
joint contractures
joint deformities (may develop over time)
arthrogryposis (severe form)

Prenatal Manifestations Movement:
decreased fetal movement (severe form)

Laboratory Abnormalities:
normal or mildly increased serum creatine kinase

Head And Neck Ears:
low-set ears (severe form)

Skeletal Hands:
clenched hands (severe form)

Clinical features from OMIM:

256030

UMLS symptoms related to Nemaline Myopathy 2:


generalized muscle weakness, waddling gait, facial paresis

GenomeRNAi Phenotypes related to Nemaline Myopathy 2 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased substrate adherent cell growth GR00193-A-1 9.1 ADORA1 ADORA2B ADORA3 TTN
2 Decreased substrate adherent cell growth GR00193-A-3 9.1 ADORA1 ADORA2B

MGI Mouse Phenotypes related to Nemaline Myopathy 2:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.07 ADORA1 ADORA2A ADORA2B ADORA3 NEB POU5F1
2 homeostasis/metabolism MP:0005376 9.96 ADORA1 ADORA2A ADORA2B ADORA3 CALR NEB
3 mortality/aging MP:0010768 9.93 ADORA1 ADORA2B CALR NANOG NEB POU5F1
4 embryo MP:0005380 9.87 ADORA2B CALR NANOG POU5F1 RET RIF1
5 muscle MP:0005369 9.5 ADORA2A CALR NEB RET TPM3 TTN
6 nervous system MP:0003631 9.28 ADORA1 ADORA2A ADORA2B CALR POU5F1 PROKR2

Drugs & Therapeutics for Nemaline Myopathy 2

Search Clinical Trials , NIH Clinical Center for Nemaline Myopathy 2

Genetic Tests for Nemaline Myopathy 2

Genetic tests related to Nemaline Myopathy 2:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 2 30 NEB
2 Nemaline Myopathy 2, Autosomal Recessive 30

Anatomical Context for Nemaline Myopathy 2

MalaCards organs/tissues related to Nemaline Myopathy 2:

42
Skeletal Muscle, Eye, Bone

Publications for Nemaline Myopathy 2

Articles related to Nemaline Myopathy 2:

(show all 13)
# Title Authors Year
1
Lethal multiple pterygium syndrome: A severe phenotype associated with a novel mutation in the nebulin gene. ( 28336317 )
2017
2
Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth. ( 26578207 )
2015
3
Nebulin interactions with actin and tropomyosin are altered by disease-causing mutations. ( 25110572 )
2014
4
Mutation update: the spectra of nebulin variants and associated myopathies. ( 25205138 )
2014
5
Carrier state for the nebulin exon 55 deletion and abnormal prenatal ultrasound findings as potential signs of nemaline myopathy. ( 22367672 )
2012
6
Clinical utility gene card for: nemaline myopathy. ( 22510848 )
2012
7
Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency. ( 19346529 )
2009
8
The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence. ( 19232495 )
2009
9
Distal myopathy caused by homozygous missense mutations in the nebulin gene. ( 17525139 )
2007
10
Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene. ( 15221447 )
2004
11
Mutations in the nebulin gene can cause severe congenital nemaline myopathy. ( 12207937 )
2002
12
Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. ( 10051637 )
1999
13
40th ENMC Sponsored International Workshop: Nemaline Myopathy. 2-4 February 1996, Naarden, The Netherlands. ( 8938704 )
1996

Variations for Nemaline Myopathy 2

ClinVar genetic disease variations for Nemaline Myopathy 2:

6 (show top 50) (show all 2261)
# Gene Variation Type Significance SNP ID Assembly Location
1 NEB NM_001271208.1(NEB): c.22584+1G> C single nucleotide variant Pathogenic rs1057515575 GRCh38 Chromosome 2, 151524310: 151524310
2 NEB NM_004543.4(NEB): c.7432-2025_7536+372del deletion Pathogenic GRCh37 Chromosome 2, 152502272: 152504773
3 NEB NEB, 2-BP DEL, AG, EX172 deletion Pathogenic
4 NEB NM_004543.4(NEB): c.7432-2025_7536+372del deletion Pathogenic GRCh38 Chromosome 2, 151645758: 151648259
5 NEB NM_001271208.1(NEB): c.25279G> T (p.Glu8427Ter) single nucleotide variant Pathogenic rs121913662 GRCh37 Chromosome 2, 152347009: 152347009
6 NEB NM_001271208.1(NEB): c.25279G> T (p.Glu8427Ter) single nucleotide variant Pathogenic rs121913662 GRCh38 Chromosome 2, 151490495: 151490495
7 NEB NM_001271208.1(NEB): c.22584+1G> C single nucleotide variant Pathogenic rs1057515575 GRCh37 Chromosome 2, 152380824: 152380824
8 NEB LRG_202t1: c.24792del deletion Pathogenic
9 NEB NM_001271208.1(NEB): c.23500_23503dupGTTT (p.Leu7835Cysfs) duplication Pathogenic rs1057515574 GRCh38 Chromosome 2, 151508058: 151508061
10 NEB NM_001271208.1(NEB): c.22746delG (p.Met7582Ilefs) deletion Pathogenic rs1057515573 GRCh37 Chromosome 2, 152375533: 152375533
11 NEB NM_001271208.1(NEB): c.22746delG (p.Met7582Ilefs) deletion Pathogenic rs1057515573 GRCh38 Chromosome 2, 151519019: 151519019
12 NEB NM_001271208.1(NEB): c.23500_23503dupGTTT (p.Leu7835Cysfs) duplication Pathogenic rs1057515574 GRCh37 Chromosome 2, 152364572: 152364575
13 NEB NM_001271208.1(NEB): c.11215A> C (p.Lys3739Gln) single nucleotide variant Uncertain significance rs267598922 NCBI36 Chromosome 2, 152180836: 152180836
14 NEB NM_001271208.1(NEB): c.6507G> A (p.Lys2169=) single nucleotide variant Likely benign rs267598923 GRCh37 Chromosome 2, 152512526: 152512526
15 NEB NM_001271208.1(NEB): c.6507G> A (p.Lys2169=) single nucleotide variant Likely benign rs267598923 GRCh38 Chromosome 2, 151656012: 151656012
16 NEB NM_001271208.1(NEB): c.6507G> A (p.Lys2169=) single nucleotide variant Likely benign rs267598923 NCBI36 Chromosome 2, 152220772: 152220772
17 NEB NM_001271208.1(NEB): c.22077G> A (p.Lys7359=) single nucleotide variant Likely benign rs267598918 GRCh37 Chromosome 2, 152382750: 152382750
18 NEB NM_001271208.1(NEB): c.22077G> A (p.Lys7359=) single nucleotide variant Likely benign rs267598918 GRCh38 Chromosome 2, 151526236: 151526236
19 NEB NM_001271208.1(NEB): c.22077G> A (p.Lys7359=) single nucleotide variant Likely benign rs267598918 NCBI36 Chromosome 2, 152090996: 152090996
20 NEB NM_001271208.1(NEB): c.18953C> T (p.Pro6318Leu) single nucleotide variant Uncertain significance rs267598920 GRCh37 Chromosome 2, 152418667: 152418667
21 NEB NM_001271208.1(NEB): c.18953C> T (p.Pro6318Leu) single nucleotide variant Uncertain significance rs267598920 GRCh38 Chromosome 2, 151562153: 151562153
22 NEB NM_001271208.1(NEB): c.18953C> T (p.Pro6318Leu) single nucleotide variant Uncertain significance rs267598920 NCBI36 Chromosome 2, 152126913: 152126913
23 NEB NM_001271208.1(NEB): c.11215A> C (p.Lys3739Gln) single nucleotide variant Uncertain significance rs267598922 GRCh37 Chromosome 2, 152472590: 152472590
24 NEB NM_001271208.1(NEB): c.11215A> C (p.Lys3739Gln) single nucleotide variant Uncertain significance rs267598922 GRCh38 Chromosome 2, 151616076: 151616076
25 NEB NM_004543.4(NEB): c.4834C> T (p.Arg1612Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs200545007 GRCh37 Chromosome 2, 152522801: 152522801
26 NEB NM_004543.4(NEB): c.4834C> T (p.Arg1612Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs200545007 GRCh38 Chromosome 2, 151666287: 151666287
27 NEB NM_004543.4(NEB): c.4834C> T (p.Arg1612Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs200545007 NCBI36 Chromosome 2, 152231047: 152231047
28 NEB NM_001271208.1(NEB): c.772G> A (p.Asp258Asn) single nucleotide variant Uncertain significance rs267598926 GRCh37 Chromosome 2, 152573980: 152573980
29 NEB NM_001271208.1(NEB): c.772G> A (p.Asp258Asn) single nucleotide variant Uncertain significance rs267598926 GRCh38 Chromosome 2, 151717466: 151717466
30 NEB NM_001271208.1(NEB): c.772G> A (p.Asp258Asn) single nucleotide variant Uncertain significance rs267598926 NCBI36 Chromosome 2, 152282226: 152282226
31 NEB NM_001271208.1(NEB): c.12147G> A (p.Lys4049=) single nucleotide variant Benign/Likely benign rs149639365 GRCh37 Chromosome 2, 152466506: 152466506
32 NEB NM_001271208.1(NEB): c.12147G> A (p.Lys4049=) single nucleotide variant Benign/Likely benign rs149639365 GRCh38 Chromosome 2, 151609992: 151609992
33 NEB NM_001271208.1(NEB): c.1152+1G> A single nucleotide variant Pathogenic rs398124167 GRCh37 Chromosome 2, 152563394: 152563394
34 NEB NM_001271208.1(NEB): c.1152+1G> A single nucleotide variant Pathogenic rs398124167 GRCh38 Chromosome 2, 151706880: 151706880
35 NEB NM_004543.4(NEB): c.12C> T (p.Asp4=) single nucleotide variant Conflicting interpretations of pathogenicity rs117178114 GRCh37 Chromosome 2, 152589659: 152589659
36 NEB NM_004543.4(NEB): c.12C> T (p.Asp4=) single nucleotide variant Conflicting interpretations of pathogenicity rs117178114 GRCh38 Chromosome 2, 151733145: 151733145
37 NEB NM_001271208.1(NEB): c.19455G> A (p.Lys6485=) single nucleotide variant Conflicting interpretations of pathogenicity rs182847302 GRCh37 Chromosome 2, 152410513: 152410513
38 NEB NM_001271208.1(NEB): c.19455G> A (p.Lys6485=) single nucleotide variant Conflicting interpretations of pathogenicity rs182847302 GRCh38 Chromosome 2, 151553999: 151553999
39 NEB NM_004543.4(NEB): c.15364-4T> A single nucleotide variant Benign/Likely benign rs199791504 GRCh37 Chromosome 2, 152402516: 152402516
40 NEB NM_004543.4(NEB): c.15364-4T> A single nucleotide variant Benign/Likely benign rs199791504 GRCh38 Chromosome 2, 151546002: 151546002
41 NEB NM_004543.4(NEB): c.16443C> T (p.Asn5481=) single nucleotide variant Benign/Likely benign rs149510427 GRCh37 Chromosome 2, 152387592: 152387592
42 NEB NM_004543.4(NEB): c.16443C> T (p.Asn5481=) single nucleotide variant Benign/Likely benign rs149510427 GRCh38 Chromosome 2, 151531078: 151531078
43 NEB NM_001271208.1(NEB): c.169_183delCTGGCACAGCCAGCA (p.Leu57_Ala61del) deletion Benign rs377452683 GRCh37 Chromosome 2, 152584316: 152584330
44 NEB NM_001271208.1(NEB): c.169_183delCTGGCACAGCCAGCA (p.Leu57_Ala61del) deletion Benign rs377452683 GRCh38 Chromosome 2, 151727802: 151727816
45 NEB NM_001271208.1(NEB): c.1782+4_1782+5del deletion Uncertain significance rs398124168 GRCh37 Chromosome 2, 152551031: 152551032
46 NEB NM_001271208.1(NEB): c.1782+4_1782+5del deletion Uncertain significance rs398124168 GRCh38 Chromosome 2, 151694517: 151694518
47 NEB NM_001271208.1(NEB): c.23383A> G (p.Asn7795Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs201189784 GRCh37 Chromosome 2, 152369315: 152369315
48 NEB NM_001271208.1(NEB): c.23383A> G (p.Asn7795Asp) single nucleotide variant Conflicting interpretations of pathogenicity rs201189784 GRCh38 Chromosome 2, 151512801: 151512801
49 NEB NM_001271208.1(NEB): c.23753C> T (p.Ser7918Leu) single nucleotide variant Uncertain significance rs202191938 GRCh37 Chromosome 2, 152362681: 152362681
50 NEB NM_001271208.1(NEB): c.23753C> T (p.Ser7918Leu) single nucleotide variant Uncertain significance rs202191938 GRCh38 Chromosome 2, 151506167: 151506167

Expression for Nemaline Myopathy 2

Search GEO for disease gene expression data for Nemaline Myopathy 2.

Pathways for Nemaline Myopathy 2

GO Terms for Nemaline Myopathy 2

Cellular components related to Nemaline Myopathy 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.63 ADORA1 ADORA2A ADORA2B ADORA3 PROKR2 RET
2 axolemma GO:0030673 8.96 ADORA1 ADORA2A
3 asymmetric synapse GO:0032279 8.62 ADORA1 ADORA2A

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

# Name GO ID Score Top Affiliating Genes
1 negative regulation of cell proliferation GO:0008285 9.67 ADORA1 ADORA2A ADORA3 GTPBP4
2 positive regulation of gene expression GO:0010628 9.62 CALR POU5F1 RET TTN
3 activation of adenylate cyclase activity GO:0007190 9.4 ADORA2B ADORA3
4 relaxation of vascular smooth muscle GO:0060087 9.26 ADORA1 ADORA2B
5 endodermal cell fate specification GO:0001714 9.16 NANOG POU5F1
6 muscle filament sliding GO:0030049 9.13 NEB TPM3 TTN
7 adenosine receptor signaling pathway GO:0001973 8.92 ADORA1 ADORA2A ADORA2B ADORA3

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

# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor activity GO:0004930 9.35 ADORA1 ADORA2A ADORA2B ADORA3 PROKR2
2 G protein-coupled adenosine receptor activity GO:0001609 8.92 ADORA1 ADORA2A ADORA2B ADORA3

Sources for Nemaline Myopathy 2

3 CDC
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
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31 HGMD
32 HMDB
33 HPO
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63 PubMed
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70 SNOMED-CT via HPO
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