MCID: NML004
MIFTS: 33

Nemaline Myopathy 3

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

Aliases & Classifications for Nemaline Myopathy 3

MalaCards integrated aliases for Nemaline Myopathy 3:

Name: Nemaline Myopathy 3 57 12 75 29 6 73
Myopathy, Actin, Congenital, with Excess of Thin Myofilaments 57 75 29 13 6
Myopathy, Actin, Congenital, with Cores 57 29 13 6
Nemaline Myopathy 3, Autosomal Dominant or Recessive 57 12 6
Nem3 57 12 75
Congenital Myopathy with Excess of Thin Filaments 59
Nemaline Myopathy 3 with Intranuclear Rods 75
Actin Myopathy Congenital with Cores 75
Acta1-Related Nemaline Myopathy 75
Actin-Accumulation Myopathy 73
Myopathy, Nemaline, Type 3 40
Nemaline Myopathy, Type 3 76
Actin Myopathy 59
Mpcetm 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
genetic heterogeneity
highly variable phenotype
slowly or nonprogressive
death in childhood often results from respiratory insufficiency
onset usually in childhood (infancy to teens)
rare adult onset


HPO:

32
nemaline myopathy 3:
Onset and clinical course phenotypic variability
Inheritance heterogeneous autosomal recessive inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Nemaline Myopathy 3

OMIM : 57 Nemaline myopathy is a form of congenital myopathy characterized by abnormal thread- or rod-like structures in muscle fibers on histologic examination ('nema' is Greek for 'thread'). The clinical phenotype is highly variable, with differing age at onset and severity. Muscle weakness typically involves proximal muscles, with involvement of the facial, bulbar, and respiratory muscles (Ilkovski et al., 2001). Attempts at classification of nemaline myopathies into clinical subtypes have been complicated by the overlap of clinical features and a continuous phenotypic spectrum of disease (North et al., 1997; Wallgren-Pettersson et al., 1999; Ryan et al., 2001; Sanoudou and Beggs, 2001). In general, 2 clinical groups can be readily distinguished: 'typical' and 'severe.' Typical nemaline myopathy is the most common form, presenting as infantile hypotonia and muscle weakness. It is slowly progressive or nonprogressive, and most adults achieve ambulation. The severe form of the disorder is characterized by absence of spontaneous movement or respiration at birth, arthrogryposis, and death in the first months of life. Much less commonly, late-childhood or even adult-onset can occur. However, adult-onset nemaline myopathy is usually not familial and may represent a different disease (Wallgren-Pettersson et al., 1999; Sanoudou and Beggs, 2001). Myopathy caused by mutations in the ACTA1 gene can show a range of clinical and pathologic phenotypes. Some patients have classic rods, whereas others may also show intranuclear rods, clumped filaments, cores, or fiber-type disproportion (see 255310), all of which are nonspecific pathologic findings and not pathognomonic of a specific congenital myopathy. The spectrum of clinical phenotypes caused by mutations in ACTA1 may result from different mutations, modifying factors affecting the severity of the disorder, variability in clinical care, or a combination of these factors (Nowak et al., 1999; Kaindl et al., 2004). (161800)

MalaCards based summary : Nemaline Myopathy 3, also known as myopathy, actin, congenital, with excess of thin myofilaments, is related to van der woude syndrome 1 and actin-accumulation myopathy, and has symptoms including waddling gait, facial paresis and generalized muscle weakness. An important gene associated with Nemaline Myopathy 3 is ACTA1 (Actin, Alpha 1, Skeletal Muscle). Related phenotypes are high palate and retrognathia

Disease Ontology : 12 A nemaline myopathy that has material basis in homozygous, compound heterozygous, or heterozygous mutation in the ACTA1 gene on chromosome 1q42.

UniProtKB/Swiss-Prot : 75 Myopathy, actin, congenital, with excess of thin myofilaments: A congenital muscular disorder characterized at histological level by areas of sarcoplasm devoid of normal myofibrils and mitochondria, and replaced with dense masses of thin filaments. Central cores, rods, ragged red fibers, and necrosis are absent. Nemaline myopathy 3: 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.

Related Diseases for Nemaline Myopathy 3

Graphical network of the top 20 diseases related to Nemaline Myopathy 3:



Diseases related to Nemaline Myopathy 3

Symptoms & Phenotypes for Nemaline Myopathy 3

Symptoms via clinical synopsis from OMIM:

57
Abdomen Gastrointestinal:
dysphagia
poor feeding due to muscle weakness

Respiratory:
respiratory insufficiency due to muscle weakness

Skeletal Feet:
pes cavus

Growth Other:
slender build

Head And Neck Mouth:
high-arched palate
tent-shaped mouth

Head And Neck Eyes:
extraocular muscles are not involved

Cardiovascular Heart:
dilated cardiomyopathy (rare)

Prenatal Manifestations Movement:
decreased fetal movement (severe form)

Laboratory Abnormalities:
normal or mildly increased serum creatine kinase

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

Head And Neck Face:
retrognathia
myopathic facies
facial muscle weakness
elongated face
expressionless face

Muscle Soft Tissue:
type 1 muscle fiber predominance
frequent falls
neck muscle weakness
facial muscle weakness
distal limb muscle weakness occurs later
more
Neurologic Central Nervous System:
areflexia
hyporeflexia
delayed motor development
severe form may never achieve sitting or walking
absent gag reflex
more
Skeletal:
joint contractures
joint deformities (may develop over time)
arthrogryposis (severe form)

Head And Neck Neck:
neck flexor muscle weakness

Neurologic Peripheral Nervous System:
hyperreflexia (uncommon)

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (severe form)


Clinical features from OMIM:

161800

Human phenotypes related to Nemaline Myopathy 3:

32 (show all 36)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 retrognathia 32 HP:0000278
3 mask-like facies 32 HP:0000298
4 hyporeflexia 32 HP:0001265
5 motor delay 32 HP:0001270
6 hypertonia 32 occasional (7.5%) HP:0001276
7 bulbar palsy 32 HP:0001283
8 areflexia 32 HP:0001284
9 neonatal hypotonia 32 HP:0001319
10 hyperreflexia 32 occasional (7.5%) HP:0001347
11 slender build 32 HP:0001533
12 decreased fetal movement 32 HP:0001558
13 polyhydramnios 32 HP:0001561
14 dilated cardiomyopathy 32 occasional (7.5%) HP:0001644
15 pes cavus 32 HP:0001761
16 dysphagia 32 HP:0002015
17 myopathic facies 32 HP:0002058
18 rigidity 32 occasional (7.5%) HP:0002063
19 frequent falls 32 HP:0002359
20 waddling gait 32 HP:0002515
21 scoliosis 32 HP:0002650
22 respiratory insufficiency due to muscle weakness 32 HP:0002747
23 arthrogryposis multiplex congenita 32 HP:0002804
24 spinal rigidity 32 HP:0003306
25 hyperlordosis 32 HP:0003307
26 generalized muscle weakness 32 HP:0003324
27 emg 32 HP:0003445
28 limb muscle weakness 32 HP:0003690
29 proximal muscle weakness 32 HP:0003701
30 neck flexor weakness 32 HP:0003722
31 nemaline bodies 32 HP:0003798
32 type 1 muscle fiber predominance 32 HP:0003803
33 late-onset distal muscle weakness 32 HP:0003810
34 mildly elevated creatine phosphokinase 32 HP:0008180
35 feeding difficulties in infancy 32 HP:0008872
36 facial palsy 32 HP:0010628

UMLS symptoms related to Nemaline Myopathy 3:


waddling gait, facial paresis, generalized muscle weakness

Drugs & Therapeutics for Nemaline Myopathy 3

Search Clinical Trials , NIH Clinical Center for Nemaline Myopathy 3

Genetic Tests for Nemaline Myopathy 3

Genetic tests related to Nemaline Myopathy 3:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 3 29 ACTA1
2 Myopathy, Actin, Congenital, with Excess of Thin Myofilaments 29
3 Myopathy, Actin, Congenital, with Cores 29

Anatomical Context for Nemaline Myopathy 3

Publications for Nemaline Myopathy 3

Articles related to Nemaline Myopathy 3:

# Title Authors Year
1
Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1-related nemaline myopathy (NEM3). ( 29328520 )
2018
2
Clinical and HistologicA Findings in ACTA1-Related Nemaline Myopathy: Case Series and Review of the Literature. ( 28780987 )
2017

Variations for Nemaline Myopathy 3

UniProtKB/Swiss-Prot genetic disease variations for Nemaline Myopathy 3:

75 (show top 50) (show all 77)
# Symbol AA change Variation ID SNP ID
1 ACTA1 p.Gly17Arg VAR_011680 rs121909521
2 ACTA1 p.Leu96Pro VAR_011681 rs121909519
3 ACTA1 p.Asn117Ser VAR_011682 rs121909520
4 ACTA1 p.Ile138Met VAR_011683 rs121909526
5 ACTA1 p.Val165Leu VAR_011684 rs121909522
6 ACTA1 p.Glu261Val VAR_011685 rs121909523
7 ACTA1 p.Gly270Cys VAR_011686 rs121909525
8 ACTA1 p.Val372Phe VAR_011687
9 ACTA1 p.Met134Val VAR_013470
10 ACTA1 p.Met271Arg VAR_013471
11 ACTA1 p.His42Tyr VAR_015579
12 ACTA1 p.Gly184Asp VAR_015580
13 ACTA1 p.Arg185Gly VAR_015581
14 ACTA1 p.Arg185Cys VAR_015582
15 ACTA1 p.Arg258His VAR_015583
16 ACTA1 p.Gln265Leu VAR_015584
17 ACTA1 p.Asn282Lys VAR_015585
18 ACTA1 p.Asp288Gly VAR_015586
19 ACTA1 p.Ile359Leu VAR_015587 rs121909524
20 ACTA1 p.Asp3Tyr VAR_062424 rs121909527
21 ACTA1 p.Asp27Asn VAR_062425
22 ACTA1 p.Val37Leu VAR_062426
23 ACTA1 p.Pro40Leu VAR_062427
24 ACTA1 p.Gln43Arg VAR_062428
25 ACTA1 p.Gly44Val VAR_062429
26 ACTA1 p.Val45Phe VAR_062430 rs398123562
27 ACTA1 p.Ile66Asn VAR_062431
28 ACTA1 p.Thr68Ile VAR_062432
29 ACTA1 p.Glu74Lys VAR_062433
30 ACTA1 p.His75Leu VAR_062434
31 ACTA1 p.His75Arg VAR_062435
32 ACTA1 p.Ile77Leu VAR_062436
33 ACTA1 p.Thr79Ala VAR_062437
34 ACTA1 p.Glu85Lys VAR_062438
35 ACTA1 p.Ala116Thr VAR_062439
36 ACTA1 p.Asn117Thr VAR_062440
37 ACTA1 p.Arg118His VAR_062441
38 ACTA1 p.Val136Ala VAR_062442
39 ACTA1 p.Ala140Pro VAR_062443
40 ACTA1 p.Leu142Pro VAR_062444
41 ACTA1 p.Gly148Asp VAR_062445
42 ACTA1 p.Thr150Asn VAR_062446
43 ACTA1 p.Asp156Asn VAR_062447
44 ACTA1 p.Val165Met VAR_062448 rs121909522
45 ACTA1 p.Ala172Gly VAR_062449
46 ACTA1 p.Asp181Gly VAR_062450
47 ACTA1 p.Asp181His VAR_062451
48 ACTA1 p.Asp181Asn VAR_062452
49 ACTA1 p.Arg185Asp VAR_062453
50 ACTA1 p.Arg185Ser VAR_062454

ClinVar genetic disease variations for Nemaline Myopathy 3:

6
(show top 50) (show all 120)
# Gene Variation Type Significance SNP ID Assembly Location
1 ACTA1 NM_001100.3(ACTA1): c.287T> C (p.Leu96Pro) single nucleotide variant Pathogenic rs121909519 GRCh37 Chromosome 1, 229568470: 229568470
2 ACTA1 NM_001100.3(ACTA1): c.287T> C (p.Leu96Pro) single nucleotide variant Pathogenic rs121909519 GRCh38 Chromosome 1, 229432723: 229432723
3 ACTA1 NM_001100.3(ACTA1): c.350A> G (p.Asn117Ser) single nucleotide variant Pathogenic rs121909520 GRCh37 Chromosome 1, 229568407: 229568407
4 ACTA1 NM_001100.3(ACTA1): c.350A> G (p.Asn117Ser) single nucleotide variant Pathogenic rs121909520 GRCh38 Chromosome 1, 229432660: 229432660
5 ACTA1 NM_001100.3(ACTA1): c.49G> C (p.Gly17Arg) single nucleotide variant Pathogenic rs121909521 GRCh37 Chromosome 1, 229568814: 229568814
6 ACTA1 NM_001100.3(ACTA1): c.49G> C (p.Gly17Arg) single nucleotide variant Pathogenic rs121909521 GRCh38 Chromosome 1, 229433067: 229433067
7 ACTA1 NM_001100.3(ACTA1): c.493G> T (p.Val165Leu) single nucleotide variant Pathogenic rs121909522 GRCh37 Chromosome 1, 229568140: 229568140
8 ACTA1 NM_001100.3(ACTA1): c.493G> T (p.Val165Leu) single nucleotide variant Pathogenic rs121909522 GRCh38 Chromosome 1, 229432393: 229432393
9 ACTA1 NM_001100.3(ACTA1): c.782A> T (p.Glu261Val) single nucleotide variant Pathogenic rs121909523 GRCh37 Chromosome 1, 229567767: 229567767
10 ACTA1 NM_001100.3(ACTA1): c.782A> T (p.Glu261Val) single nucleotide variant Pathogenic rs121909523 GRCh38 Chromosome 1, 229432020: 229432020
11 ACTA1 NM_001100.3(ACTA1): c.1075A> C (p.Ile359Leu) single nucleotide variant Pathogenic rs121909524 GRCh37 Chromosome 1, 229567305: 229567305
12 ACTA1 NM_001100.3(ACTA1): c.1075A> C (p.Ile359Leu) single nucleotide variant Pathogenic rs121909524 GRCh38 Chromosome 1, 229431558: 229431558
13 ACTA1 NM_001100.3(ACTA1): c.808G> T (p.Gly270Cys) single nucleotide variant Pathogenic rs121909525 GRCh37 Chromosome 1, 229567741: 229567741
14 ACTA1 NM_001100.3(ACTA1): c.808G> T (p.Gly270Cys) single nucleotide variant Pathogenic rs121909525 GRCh38 Chromosome 1, 229431994: 229431994
15 ACTA1 NM_001100.3(ACTA1): c.414C> G (p.Ile138Met) single nucleotide variant Pathogenic rs121909526 GRCh37 Chromosome 1, 229568343: 229568343
16 ACTA1 NM_001100.3(ACTA1): c.414C> G (p.Ile138Met) single nucleotide variant Pathogenic rs121909526 GRCh38 Chromosome 1, 229432596: 229432596
17 ACTA1 NM_001100.3(ACTA1): c.7G> T (p.Asp3Tyr) single nucleotide variant Pathogenic rs121909527 GRCh37 Chromosome 1, 229568856: 229568856
18 ACTA1 NM_001100.3(ACTA1): c.7G> T (p.Asp3Tyr) single nucleotide variant Pathogenic rs121909527 GRCh38 Chromosome 1, 229433109: 229433109
19 ACTA1 NM_001100.3(ACTA1): c.1007A> C (p.Glu336Ala) single nucleotide variant Pathogenic rs121909528 GRCh37 Chromosome 1, 229567373: 229567373
20 ACTA1 NM_001100.3(ACTA1): c.1007A> C (p.Glu336Ala) single nucleotide variant Pathogenic rs121909528 GRCh38 Chromosome 1, 229431626: 229431626
21 ACTA1 NM_001100.3(ACTA1): c.493G> A (p.Val165Met) single nucleotide variant Pathogenic rs121909522 GRCh37 Chromosome 1, 229568140: 229568140
22 ACTA1 NM_001100.3(ACTA1): c.493G> A (p.Val165Met) single nucleotide variant Pathogenic rs121909522 GRCh38 Chromosome 1, 229432393: 229432393
23 ACTA1 NM_001100.3(ACTA1): c.984G> C (p.Lys328Asn) single nucleotide variant Pathogenic rs398122936 GRCh37 Chromosome 1, 229567474: 229567474
24 ACTA1 NM_001100.3(ACTA1): c.984G> C (p.Lys328Asn) single nucleotide variant Pathogenic rs398122936 GRCh38 Chromosome 1, 229431727: 229431727
25 ACTA1 NM_001100.3(ACTA1): c.133G> T (p.Val45Phe) single nucleotide variant Likely pathogenic rs398123562 GRCh37 Chromosome 1, 229568624: 229568624
26 ACTA1 NM_001100.3(ACTA1): c.133G> T (p.Val45Phe) single nucleotide variant Likely pathogenic rs398123562 GRCh38 Chromosome 1, 229432877: 229432877
27 ACTA1 NM_001100.3(ACTA1): c.442G> A (p.Gly148Ser) single nucleotide variant Likely pathogenic rs398123563 GRCh37 Chromosome 1, 229568315: 229568315
28 ACTA1 NM_001100.3(ACTA1): c.442G> A (p.Gly148Ser) single nucleotide variant Likely pathogenic rs398123563 GRCh38 Chromosome 1, 229432568: 229432568
29 ACTA1 NM_001100.3(ACTA1): c.1074G> T (p.Trp358Cys) single nucleotide variant Pathogenic rs587777354 GRCh37 Chromosome 1, 229567306: 229567306
30 ACTA1 NM_001100.3(ACTA1): c.1074G> T (p.Trp358Cys) single nucleotide variant Pathogenic rs587777354 GRCh38 Chromosome 1, 229431559: 229431559
31 ACTA1 NM_001100.3(ACTA1): c.413T> A (p.Ile138Asn) single nucleotide variant Likely pathogenic rs587780271 GRCh37 Chromosome 1, 229568344: 229568344
32 ACTA1 NM_001100.3(ACTA1): c.413T> A (p.Ile138Asn) single nucleotide variant Likely pathogenic rs587780271 GRCh38 Chromosome 1, 229432597: 229432597
33 ACTA1 NM_001100.3(ACTA1): c.515C> A (p.Ala172Glu) single nucleotide variant Pathogenic rs587780272 GRCh37 Chromosome 1, 229568118: 229568118
34 ACTA1 NM_001100.3(ACTA1): c.515C> A (p.Ala172Glu) single nucleotide variant Pathogenic rs587780272 GRCh38 Chromosome 1, 229432371: 229432371
35 ACTA1 NM_001100.3(ACTA1): c.536G> T (p.Arg179Leu) single nucleotide variant Likely pathogenic rs727503797 GRCh37 Chromosome 1, 229568097: 229568097
36 ACTA1 NM_001100.3(ACTA1): c.536G> T (p.Arg179Leu) single nucleotide variant Likely pathogenic rs727503797 GRCh38 Chromosome 1, 229432350: 229432350
37 ACTA1 NM_001100.3(ACTA1): c.142G> A (p.Gly48Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs794727488 GRCh37 Chromosome 1, 229568615: 229568615
38 ACTA1 NM_001100.3(ACTA1): c.142G> A (p.Gly48Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs794727488 GRCh38 Chromosome 1, 229432868: 229432868
39 ACTA1 NM_001100.3(ACTA1): c.923A> G (p.Tyr308Cys) single nucleotide variant Likely pathogenic rs878854374 GRCh38 Chromosome 1, 229431788: 229431788
40 ACTA1 NM_001100.3(ACTA1): c.923A> G (p.Tyr308Cys) single nucleotide variant Likely pathogenic rs878854374 GRCh37 Chromosome 1, 229567535: 229567535
41 ACTA1 NM_001100.3(ACTA1): c.808G> C (p.Gly270Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121909525 GRCh37 Chromosome 1, 229567741: 229567741
42 ACTA1 NM_001100.3(ACTA1): c.808G> C (p.Gly270Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121909525 GRCh38 Chromosome 1, 229431994: 229431994
43 ACTA1 NM_001100.3(ACTA1): c.617-5C> T single nucleotide variant Benign/Likely benign rs199804338 GRCh38 Chromosome 1, 229432190: 229432190
44 ACTA1 NM_001100.3(ACTA1): c.617-5C> T single nucleotide variant Benign/Likely benign rs199804338 GRCh37 Chromosome 1, 229567937: 229567937
45 ACTA1 NM_001100.3(ACTA1): c.453C> A (p.Thr151=) single nucleotide variant Benign/Likely benign rs76030344 GRCh37 Chromosome 1, 229568304: 229568304
46 ACTA1 NM_001100.3(ACTA1): c.453C> A (p.Thr151=) single nucleotide variant Benign/Likely benign rs76030344 GRCh38 Chromosome 1, 229432557: 229432557
47 ACTA1 NM_001100.3(ACTA1): c.521C> T (p.Pro174Leu) single nucleotide variant Likely pathogenic rs1057519311 GRCh37 Chromosome 1, 229568112: 229568112
48 ACTA1 NM_001100.3(ACTA1): c.521C> T (p.Pro174Leu) single nucleotide variant Likely pathogenic rs1057519311 GRCh38 Chromosome 1, 229432365: 229432365
49 ACTA1 NM_001100.3(ACTA1): c.676G> C (p.Glu226Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs1057521118 GRCh37 Chromosome 1, 229567873: 229567873
50 ACTA1 NM_001100.3(ACTA1): c.676G> C (p.Glu226Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs1057521118 GRCh38 Chromosome 1, 229432126: 229432126

Expression for Nemaline Myopathy 3

Search GEO for disease gene expression data for Nemaline Myopathy 3.

Pathways for Nemaline Myopathy 3

GO Terms for Nemaline Myopathy 3

Sources for Nemaline Myopathy 3

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