NEM5
MCID: NML006
MIFTS: 42

Nemaline Myopathy 5 (NEM5)

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

Aliases & Classifications for Nemaline Myopathy 5

MalaCards integrated aliases for Nemaline Myopathy 5:

Name: Nemaline Myopathy 5 57 12 72 29 6 15 70
Amish Nemaline Myopathy 57 12 20 58 72
Nemaline Myopathy 5, Amish Type 57 12 20 29
Nem5 57 12 20 72
Anm 57 12 20 72
Nemaline Myopathy, Amish Type 57 20 13
Nemaline Myopathy, Caused by Mutation in the Troponin T1 Gene 20
Nemaline Myopathy, Amish Type; Anm 57
Tnnt1-Related Nemaline Myopathy 72
Nemaline Myopathy Amish Type 72
Myopathy, Nemaline, Type 5 39
Nemaline Myopathy, Type 5 73

Characteristics:

Orphanet epidemiological data:

58
amish nemaline myopathy
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: early childhood;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
death secondary to respiratory insufficiency
all cases occur in old order amish, lancaster county, pennsylvania


HPO:

31
nemaline myopathy 5:
Inheritance autosomal recessive inheritance
Onset and clinical course neonatal onset


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110936
OMIM® 57 605355
OMIM Phenotypic Series 57 PS161800
MeSH 44 D017696
ICD10 via Orphanet 33 G71.2
Orphanet 58 ORPHA98902
MedGen 41 C1854380
UMLS 70 C1854380

Summaries for Nemaline Myopathy 5

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 98902 Definition A type of nemaline myopathy (NM) only observed in several families of the Amish community. Clinical description It has a neonatal onset and patients present with hypotonia associated to contractures, a severe pectus carinatum, and tremor that subsides after 2-3 months of age. Etiology TNNT1 (19q13.4) is the causative gene of the Amish NM. Genetic counseling Transmission follows an autosomal recessive pattern. Prognosis Life expectancy rarely exceeds 2 years as a consequence of severe respiratory insufficiency.

MalaCards based summary : Nemaline Myopathy 5, also known as amish nemaline myopathy, is related to left bundle branch hemiblock and atrial standstill 1. An important gene associated with Nemaline Myopathy 5 is TNNT1 (Troponin T1, Slow Skeletal Type), and among its related pathways/superpathways is Striated Muscle Contraction. Affiliated tissues include skeletal muscle and brain, and related phenotypes are tremor and pectus carinatum

Disease Ontology : 12 A nemaline myopathy that has material basis in homozygous mutation in the TNNT1 gene on chromosome 19q13.

UniProtKB/Swiss-Prot : 72 Nemaline myopathy 5: 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. Nemaline myopathy type 5 is a severe and progressive form common among Old Order Amish. Affected infants display tremors with hypotonia and mild contractures of the shoulders and hips. Proximal contractures progressively weaken and a pectus carinatum deformity develops before children die of respiratory insufficiency, usually in the second year.

Wikipedia : 73 Nemaline myopathy (also called rod myopathy or nemaline rod myopathy) is a congenital, often hereditary... more...

More information from OMIM: 605355 PS161800

Related Diseases for Nemaline Myopathy 5

Graphical network of the top 20 diseases related to Nemaline Myopathy 5:



Diseases related to Nemaline Myopathy 5

Symptoms & Phenotypes for Nemaline Myopathy 5

Human phenotypes related to Nemaline Myopathy 5:

58 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
2 pectus carinatum 58 31 frequent (33%) Frequent (79-30%) HP:0000768
3 neonatal hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001319
4 emg: myopathic abnormalities 58 31 frequent (33%) Frequent (79-30%) HP:0003458
5 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
6 type 1 muscle fiber predominance 58 31 frequent (33%) Frequent (79-30%) HP:0003803
7 shoulder flexion contracture 58 31 frequent (33%) Frequent (79-30%) HP:0003044
8 hip contracture 58 31 frequent (33%) Frequent (79-30%) HP:0003273
9 proximal amyotrophy 58 31 frequent (33%) Frequent (79-30%) HP:0007126
10 progressive muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003323
11 respiratory insufficiency due to muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0002747
12 intellectual disability 58 Excluded (0%)
13 respiratory insufficiency 31 HP:0002093
14 myopathy 31 HP:0003198
15 nemaline bodies 31 HP:0003798
16 delayed gross motor development 31 HP:0002194
17 decreased hip abduction 31 HP:0003184
18 z-band streaming 31 HP:0020203

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Muscle Soft Tissue:
type 1 muscle fiber predominance
muscle weakness, progressive
tremor at birth, involving most skeletal muscle groups, especially jaw muscles and lower limb muscles
tremors subside over the first 2 to 3 months of life
muscle atrophy, progressive
more
Chest External Features:
chest wall rigidity

Skeletal:
contractures, proximal, progressive (shoulders and hips, present at birth)

Neurologic Central Nervous System:
normal intelligence
limited gross motor development

Chest Ribs Sternum Clavicles And Scapulae:
pectus carinatum, severe

Skeletal Pelvis:
limited hip abduction (less than 10 degrees by age 12 months)

Clinical features from OMIM®:

605355 (Updated 20-May-2021)

Drugs & Therapeutics for Nemaline Myopathy 5

Search Clinical Trials , NIH Clinical Center for Nemaline Myopathy 5

Genetic Tests for Nemaline Myopathy 5

Genetic tests related to Nemaline Myopathy 5:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 5 29 TNNT1
2 Nemaline Myopathy 5, Amish Type 29

Anatomical Context for Nemaline Myopathy 5

MalaCards organs/tissues related to Nemaline Myopathy 5:

40
Skeletal Muscle, Brain

Publications for Nemaline Myopathy 5

Articles related to Nemaline Myopathy 5:

(show all 12)
# Title Authors PMID Year
1
A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. 6 57
10952871 2000
2
TNNT1 nemaline myopathy: natural history and therapeutic frontier. 57
29931346 2018
3
Functional Basis of Three New Recessive Mutations of Slow Skeletal Muscle Troponin T Found in Non-Amish TNNT1 Nemaline Myopathies. 6
27429059 2016
4
Identification of a novel nemaline myopathy-causing mutation in the troponin T1 (TNNT1) gene: a case outside of the old order Amish. 6
25430424 2015
5
Nemaline myopathy caused byTNNT1 mutations in a Dutch pedigree. 6
24689076 2014
6
Cellular fate of truncated slow skeletal muscle troponin T produced by Glu180 nonsense mutation in amish nemaline myopathy. 6
15665378 2005
7
Truncation by Glu180 nonsense mutation results in complete loss of slow skeletal muscle troponin T in a lethal nemaline myopathy. 6
12732643 2003
8
Spectrum of congenital myopathies: a single centre experience. 61
23860144 2013
9
Transactivation of the human NME5 gene by Sp1 in pancreatic cancer cells. 61
22564704 2012
10
Congenital myopathies: clinical and immunohistochemical study. 61
22234203 2011
11
Congenital myopathies in Israeli families. 61
17641259 2007
12
[Nemaline myopathy--5 cases from 3 families--clinical and histological studies]. 61
557399 1977

Variations for Nemaline Myopathy 5

ClinVar genetic disease variations for Nemaline Myopathy 5:

6 (show top 50) (show all 98)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TNNT1 NM_003283.6(TNNT1):c.538G>T (p.Glu180Ter) SNV Pathogenic 12440 rs80358249 GRCh37: 19:55648544-55648544
GRCh38: 19:55137176-55137176
2 TNNT1 NM_003283.6(TNNT1):c.120dup (p.Lys41fs) Duplication Pathogenic 534399 rs1555859304 GRCh37: 19:55656919-55656920
GRCh38: 19:55145551-55145552
3 TNNT1 NC_000019.10:g.(?_55140863)_(55147177_?)del Deletion Pathogenic 583940 GRCh37: 19:55652231-55658545
GRCh38: 19:55140863-55147177
4 overlap with 2 genes GRCh37/hg19 19q13.42(chr19:55652193-55665240) copy number loss Pathogenic 625672 GRCh37: 19:55652193-55665240
GRCh38:
5 overlap with 2 genes NC_000019.10:g.(?_55140863)_(55151937_?)del Deletion Pathogenic 651255 GRCh37: 19:55652231-55663305
GRCh38: 19:55140863-55151937
6 TNNT1 NM_003283.6(TNNT1):c.695dup (p.Leu233fs) Duplication Pathogenic 949099 GRCh37: 19:55645488-55645489
GRCh38: 19:55134120-55134121
7 TNNT1 NM_003283.6(TNNT1):c.353del (p.Thr118fs) Deletion Pathogenic 870626 GRCh37: 19:55652285-55652285
GRCh38: 19:55140917-55140917
8 TNNT1 NC_000019.10:g.(?_55140873)_(55147167_?)del Deletion Pathogenic 660688 GRCh37: 19:55652241-55658535
GRCh38: 19:55140873-55147167
9 TNNT1 NM_003283.6(TNNT1):c.452del (p.Lys151fs) Deletion Pathogenic 978511 GRCh37: 19:55649378-55649378
GRCh38: 19:55138010-55138010
10 TNNT1 NM_003283.6(TNNT1):c.1A>G (p.Met1Val) SNV Likely pathogenic 870625 GRCh37: 19:55658525-55658525
GRCh38: 19:55147157-55147157
11 TNNT1 NM_003283.6(TNNT1):c.606_607insTAGTG (p.Leu203Ter) Insertion Likely pathogenic 804429 rs1599875856 GRCh37: 19:55648475-55648476
GRCh38: 19:55137107-55137108
12 TNNT1 NM_003283.6(TNNT1):c.502-2A>G SNV Likely pathogenic 569105 rs1156410888 GRCh37: 19:55648582-55648582
GRCh38: 19:55137214-55137214
13 TNNT1 NM_003283.6(TNNT1):c.32+5G>A SNV Likely pathogenic 465995 rs1555859876 GRCh37: 19:55658489-55658489
GRCh38: 19:55147121-55147121
14 TNNT1 NM_003283.6(TNNT1):c.47-6C>G SNV Conflicting interpretations of pathogenicity 259031 rs375682055 GRCh37: 19:55658081-55658081
GRCh38: 19:55146713-55146713
15 TNNT1 NM_003283.6(TNNT1):c.751-5C>T SNV Conflicting interpretations of pathogenicity 259035 rs192248377 GRCh37: 19:55645300-55645300
GRCh38: 19:55133932-55133932
16 TNNT1 NM_003283.6(TNNT1):c.279A>G (p.Glu93=) SNV Conflicting interpretations of pathogenicity 31856 rs34313388 GRCh37: 19:55652584-55652584
GRCh38: 19:55141216-55141216
17 TNNT1 NM_003283.6(TNNT1):c.31_32+1del Microsatellite Conflicting interpretations of pathogenicity 497007 rs944152647 GRCh37: 19:55658493-55658495
GRCh38: 19:55147125-55147127
18 overlap with 10 genes NC_000019.9:g.(?_55644273)_(55768277_?)dup Duplication Uncertain significance 648531 GRCh37: 19:55644273-55768277
GRCh38: 19:55132905-55256909
19 TNNT1 NM_003283.6(TNNT1):c.388-11_388-8del Deletion Uncertain significance 534398 rs1555857020 GRCh37: 19:55649450-55649453
GRCh38: 19:55138082-55138085
20 TNNT1 NM_003283.6(TNNT1):c.139G>A (p.Val47Met) SNV Uncertain significance 663497 rs1599884701 GRCh37: 19:55653278-55653278
GRCh38: 19:55141910-55141910
21 TNNT1 NM_003283.6(TNNT1):c.5C>G (p.Ser2Trp) SNV Uncertain significance 1000388 GRCh37: 19:55658521-55658521
GRCh38: 19:55147153-55147153
22 TNNT1 NM_003283.6(TNNT1):c.207G>T (p.Lys69Asn) SNV Uncertain significance 1010087 GRCh37: 19:55652656-55652656
GRCh38: 19:55141288-55141288
23 TNNT1 NM_003283.6(TNNT1):c.309+6C>T SNV Uncertain significance 1015747 GRCh37: 19:55652548-55652548
GRCh38: 19:55141180-55141180
24 TNNT1 NM_003283.6(TNNT1):c.77C>A (p.Pro26His) SNV Uncertain significance 1020293 GRCh37: 19:55657831-55657831
GRCh38: 19:55146463-55146463
25 TNNT1 NM_003283.6(TNNT1):c.136G>A (p.Val46Met) SNV Uncertain significance 1022550 GRCh37: 19:55653281-55653281
GRCh38: 19:55141913-55141913
26 TNNT1 NM_003283.6(TNNT1):c.409G>A (p.Glu137Lys) SNV Uncertain significance 1023674 GRCh37: 19:55649421-55649421
GRCh38: 19:55138053-55138053
27 TNNT1 NM_003283.6(TNNT1):c.826C>T (p.Arg276Cys) SNV Uncertain significance 1028592 GRCh37: 19:55644294-55644294
GRCh38: 19:55132926-55132926
28 TNNT1 NM_003283.6(TNNT1):c.116G>A (p.Arg39His) SNV Uncertain significance 1046151 GRCh37: 19:55656924-55656924
GRCh38: 19:55145556-55145556
29 TNNT1 NM_003283.6(TNNT1):c.310-8T>A SNV Uncertain significance 1061766 GRCh37: 19:55652336-55652336
GRCh38: 19:55140968-55140968
30 TNNT1 NC_000019.10:g.(?_55140863)_(55141322_?)del Deletion Uncertain significance 534404 GRCh37: 19:55652231-55652690
GRCh38: 19:55140863-55141322
31 TNNT1 NM_003283.6(TNNT1):c.73G>A (p.Ala25Thr) SNV Uncertain significance 892902 GRCh37: 19:55658049-55658049
GRCh38: 19:55146681-55146681
32 TNNT1 NM_003283.6(TNNT1):c.33-7T>G SNV Uncertain significance 838470 GRCh37: 19:55658396-55658396
GRCh38: 19:55147028-55147028
33 TNNT1 NM_003283.6(TNNT1):c.562G>A (p.Glu188Lys) SNV Uncertain significance 847963 GRCh37: 19:55648520-55648520
GRCh38: 19:55137152-55137152
34 TNNT1 NM_003283.6(TNNT1):c.611G>A (p.Arg204Gln) SNV Uncertain significance 856207 GRCh37: 19:55648471-55648471
GRCh38: 19:55137103-55137103
35 TNNT1 NM_003283.6(TNNT1):c.387+5G>A SNV Uncertain significance 857846 GRCh37: 19:55652246-55652246
GRCh38: 19:55140878-55140878
36 TNNT1 NM_003283.6(TNNT1):c.653C>G (p.Pro218Arg) SNV Uncertain significance 859097 GRCh37: 19:55645531-55645531
GRCh38: 19:55134163-55134163
37 TNNT1 NM_003283.6(TNNT1):c.370C>T (p.Arg124Cys) SNV Uncertain significance 864639 GRCh37: 19:55652268-55652268
GRCh38: 19:55140900-55140900
38 TNNT1 NM_003283.6(TNNT1):c.550C>T (p.Arg184Cys) SNV Uncertain significance 949441 GRCh37: 19:55648532-55648532
GRCh38: 19:55137164-55137164
39 TNNT1 NM_003283.6(TNNT1):c.32+4A>T SNV Uncertain significance 952600 GRCh37: 19:55658490-55658490
GRCh38: 19:55147122-55147122
40 TNNT1 NM_003283.6(TNNT1):c.202C>T (p.Arg68Cys) SNV Uncertain significance 957494 GRCh37: 19:55652661-55652661
GRCh38: 19:55141293-55141293
41 TNNT1 NM_003283.6(TNNT1):c.460C>G (p.Leu154Val) SNV Uncertain significance 962524 GRCh37: 19:55649370-55649370
GRCh38: 19:55138002-55138002
42 TNNT1 NM_003283.6(TNNT1):c.711G>T (p.Lys237Asn) SNV Uncertain significance 962593 GRCh37: 19:55645473-55645473
GRCh38: 19:55134105-55134105
43 TNNT1 NM_003283.6(TNNT1):c.723G>A (p.Met241Ile) SNV Uncertain significance 962709 GRCh37: 19:55645461-55645461
GRCh38: 19:55134093-55134093
44 TNNT1 NM_003283.6(TNNT1):c.26A>G (p.Tyr9Cys) SNV Uncertain significance 969432 GRCh37: 19:55658500-55658500
GRCh38: 19:55147132-55147132
45 TNNT1 NM_003283.6(TNNT1):c.*129C>G SNV Uncertain significance 893672 GRCh37: 19:55644154-55644154
GRCh38: 19:55132786-55132786
46 TNNT1 NM_003283.6(TNNT1):c.*110T>C SNV Uncertain significance 893673 GRCh37: 19:55644173-55644173
GRCh38: 19:55132805-55132805
47 TNNT1 NM_003283.6(TNNT1):c.611+12G>A SNV Uncertain significance 388590 rs376456377 GRCh37: 19:55648459-55648459
GRCh38: 19:55137091-55137091
48 TNNT1 NM_003283.6(TNNT1):c.487G>A (p.Gly163Ser) SNV Uncertain significance 894347 GRCh37: 19:55649343-55649343
GRCh38: 19:55137975-55137975
49 TNNT1 NM_003283.6(TNNT1):c.366C>T (p.Arg122=) SNV Uncertain significance 894348 GRCh37: 19:55652272-55652272
GRCh38: 19:55140904-55140904
50 TNNT1 NM_003283.6(TNNT1):c.310-14T>C SNV Uncertain significance 383122 rs115663668 GRCh37: 19:55652342-55652342
GRCh38: 19:55140974-55140974

Expression for Nemaline Myopathy 5

Search GEO for disease gene expression data for Nemaline Myopathy 5.

Pathways for Nemaline Myopathy 5

Pathways related to Nemaline Myopathy 5 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.66 TNNT3 TNNT1 TNNI3

GO Terms for Nemaline Myopathy 5

Cellular components related to Nemaline Myopathy 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 troponin complex GO:0005861 8.8 TNNT3 TNNT1 TNNI3

Biological processes related to Nemaline Myopathy 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 muscle contraction GO:0006936 9.43 TNNT3 TNNT1 TNNI3
2 muscle filament sliding GO:0030049 9.33 TNNT3 TNNT1 TNNI3
3 sarcomere organization GO:0045214 9.32 TNNT3 TNNT1
4 skeletal muscle contraction GO:0003009 9.13 TNNT3 TNNT1 TNNI3
5 regulation of muscle contraction GO:0006937 8.8 TNNT3 TNNT1 TNNI3

Molecular functions related to Nemaline Myopathy 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tropomyosin binding GO:0005523 9.16 TNNT3 TNNT1
2 troponin T binding GO:0031014 8.96 TNNT1 TNNI3
3 troponin C binding GO:0030172 8.62 TNNT3 TNNI3

Sources for Nemaline Myopathy 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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