NEM2
MCID: NML003
MIFTS: 45

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 57 12 75 29 6 15 73
Nemaline Myopathy 2, Autosomal Recessive 57 12 29 13 6
Nem2 57 12 75
Neb-Related Nemaline Myopathy 75
Myopathy, Nemaline, Type 2 40
Nemaline Myopathy, Type 2 76

Characteristics:

OMIM:

57
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:

32
nemaline myopathy 2:
Onset and clinical course infantile onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Nemaline Myopathy 2

OMIM : 57 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 myopathy and 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 Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways and Signaling pathways regulating pluripotency of stem cells. Affiliated tissues include skeletal muscle, bone and eye, 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 : 75 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 : 76 Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, hereditary... more...

Related Diseases for Nemaline Myopathy 2

Diseases in the Nemaline Myopathy family:

Nemaline Myopathy 3 Nemaline Myopathy 2
Nemaline Myopathy 5 Nemaline Myopathy 6
Nemaline Myopathy 1 Nemaline Myopathy 4
Nemaline Myopathy 7 Nemaline Myopathy 8
Nemaline Myopathy 9 Nemaline Myopathy 10
Nemaline Myopathy 11, Autosomal Recessive Adult-Onset Nemaline Myopathy
Intermediate Congenital Nemaline Myopathy Severe Congenital Nemaline Myopathy

Diseases related to Nemaline Myopathy 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 myopathy 30.4 NEB TPM3 TTN
2 nemaline myopathy 10.2
3 intermediate congenital nemaline myopathy 10.2 NEB TPM3
4 childhood-onset nemaline myopathy 10.2 NEB TPM3
5 cardioneuromyopathy with hyaline masses and nemaline rods 10.2 NEB TTN
6 reducing body myopathy 10.1 NEB TTN
7 congenital structural myopathy 10.1 NEB TPM3
8 muscular disease 10.0 NEB TPM3 TTN
9 ovarian embryonal carcinoma 10.0 NANOG POU5F1
10 maturity-onset diabetes of the young, type 8, with exocrine dysfunction 10.0 NANOG POU5F1
11 venous hemangioma 10.0 NANOG POU5F1
12 phosphoglycerate dehydrogenase deficiency 9.9 NANOG POU5F1
13 multiple endocrine neoplasia, type iib 9.9 CALCA RET
14 nodular goiter 9.9 CALCA RET
15 germ cell and embryonal cancer 9.9 NANOG POU5F1
16 parathyroid gland disease 9.9 CALCA RET
17 multiple endocrine neoplasia, type iia 9.9 CALCA RET
18 parathyroid carcinoma 9.8 CALCA RET
19 endocrine organ benign neoplasm 9.8 CALCA RET
20 extragonadal seminoma 9.7 CALCA NANOG POU5F1

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



Diseases related to Nemaline Myopathy 2

Symptoms & Phenotypes for Nemaline Myopathy 2

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Nemaline Myopathy 2:

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

UMLS symptoms related to Nemaline Myopathy 2:


generalized muscle weakness, waddling gait, facial paresis

MGI Mouse Phenotypes related to Nemaline Myopathy 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.65 CALR NANOG NEB POU5F1 PROKR2 RET
2 embryo MP:0005380 9.63 CALR NANOG POU5F1 RET RIF1 TTN
3 muscle MP:0005369 9.1 CALR NEB RET TPM3 TTN ZIC1

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 29 NEB
2 Nemaline Myopathy 2, Autosomal Recessive 29

Anatomical Context for Nemaline Myopathy 2

MalaCards organs/tissues related to Nemaline Myopathy 2:

41
Skeletal Muscle, Bone, Eye, Thyroid

Publications for Nemaline Myopathy 2

Articles related to Nemaline Myopathy 2:

# Title Authors Year
1
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 2263)
# Gene Variation Type Significance SNP ID Assembly Location
1 NEB NM_004543.4(NEB): c.7432-2025_7536+372del2502 deletion Pathogenic rs80358246 GRCh37 Chromosome 2, 152502272: 152504773
2 NEB NM_004543.4(NEB): c.7432-2025_7536+372del2502 deletion Pathogenic rs80358246 GRCh38 Chromosome 2, 151645758: 151648259
3 NEB NM_001271208.1(NEB): c.22746delG (p.Met7582Ilefs) deletion Pathogenic rs1057515573 GRCh37 Chromosome 2, 152375533: 152375533
4 NEB NM_001271208.1(NEB): c.22746delG (p.Met7582Ilefs) deletion Pathogenic rs1057515573 GRCh38 Chromosome 2, 151519019: 151519019
5 NEB NM_001271208.1(NEB): c.23500_23503dupGTTT (p.Leu7835Cysfs) duplication Pathogenic rs1057515574 GRCh37 Chromosome 2, 152364572: 152364575
6 NEB NM_001271208.1(NEB): c.23500_23503dupGTTT (p.Leu7835Cysfs) duplication Pathogenic rs1057515574 GRCh38 Chromosome 2, 151508058: 151508061
7 NEB NEB, 2-BP DEL, AG, EX172 deletion Pathogenic
8 NEB NEB, 2-BP DEL, GA, EX181 deletion Pathogenic
9 NEB NM_001271208.1(NEB): c.25279G> T (p.Glu8427Ter) single nucleotide variant Pathogenic rs121913662 GRCh37 Chromosome 2, 152347009: 152347009
10 NEB NM_001271208.1(NEB): c.25279G> T (p.Glu8427Ter) single nucleotide variant Pathogenic rs121913662 GRCh38 Chromosome 2, 151490495: 151490495
11 NEB NM_001271208.1(NEB): c.22584+1G> C single nucleotide variant Pathogenic rs1057515575 GRCh37 Chromosome 2, 152380824: 152380824
12 NEB NM_001271208.1(NEB): c.22584+1G> C single nucleotide variant Pathogenic rs1057515575 GRCh38 Chromosome 2, 151524310: 151524310
13 NEB NM_001271208.1(NEB): c.22077G> A (p.Lys7359=) single nucleotide variant Likely benign rs267598918 GRCh37 Chromosome 2, 152382750: 152382750
14 NEB NM_001271208.1(NEB): c.22077G> A (p.Lys7359=) single nucleotide variant Likely benign rs267598918 GRCh38 Chromosome 2, 151526236: 151526236
15 NEB NM_001271208.1(NEB): c.22077G> A (p.Lys7359=) single nucleotide variant Likely benign rs267598918 NCBI36 Chromosome 2, 152090996: 152090996
16 NEB NM_001271208.1(NEB): c.18953C> T (p.Pro6318Leu) single nucleotide variant Uncertain significance rs267598920 GRCh37 Chromosome 2, 152418667: 152418667
17 NEB NM_001271208.1(NEB): c.18953C> T (p.Pro6318Leu) single nucleotide variant Uncertain significance rs267598920 GRCh38 Chromosome 2, 151562153: 151562153
18 NEB NM_001271208.1(NEB): c.18953C> T (p.Pro6318Leu) single nucleotide variant Uncertain significance rs267598920 NCBI36 Chromosome 2, 152126913: 152126913
19 NEB NM_001271208.1(NEB): c.11215A> C (p.Lys3739Gln) single nucleotide variant Uncertain significance rs267598922 GRCh37 Chromosome 2, 152472590: 152472590
20 NEB NM_001271208.1(NEB): c.11215A> C (p.Lys3739Gln) single nucleotide variant Uncertain significance rs267598922 GRCh38 Chromosome 2, 151616076: 151616076
21 NEB NM_001271208.1(NEB): c.11215A> C (p.Lys3739Gln) single nucleotide variant Uncertain significance rs267598922 NCBI36 Chromosome 2, 152180836: 152180836
22 NEB NM_001271208.1(NEB): c.6507G> A (p.Lys2169=) single nucleotide variant Likely benign rs267598923 GRCh37 Chromosome 2, 152512526: 152512526
23 NEB NM_001271208.1(NEB): c.6507G> A (p.Lys2169=) single nucleotide variant Likely benign rs267598923 GRCh38 Chromosome 2, 151656012: 151656012
24 NEB NM_001271208.1(NEB): c.6507G> A (p.Lys2169=) single nucleotide variant Likely benign rs267598923 NCBI36 Chromosome 2, 152220772: 152220772
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 cytoplasm GO:0005737 9.32 CALCA CALR GTPBP4 NEB POU5F1 RET

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

# Name GO ID Score Top Affiliating Genes
1 positive regulation of gene expression GO:0010628 9.56 CALR POU5F1 RET TTN
2 response to pain GO:0048265 9.16 CALCA RET
3 endodermal cell fate specification GO:0001714 8.96 NANOG POU5F1
4 muscle filament sliding GO:0030049 8.8 NEB TPM3 TTN

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

# Name GO ID Score Top Affiliating Genes
1 structural constituent of muscle GO:0008307 8.96 NEB TTN
2 actin filament binding GO:0051015 8.8 NEB TPM3 TTN

Sources for Nemaline Myopathy 2

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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