MCID: NTV001
MIFTS: 40

Native American Myopathy

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

Aliases & Classifications for Native American Myopathy

MalaCards integrated aliases for Native American Myopathy:

Name: Native American Myopathy 57 12 53 59 75 37 29 6 44 15 73
Congenital Myopathy-Cleft Palate-Malignant Hyperthermia Syndrome 53 59
Nam 57 75
Myopathy, Congenital, with Cleft Palate and Malignant Hyperthermia 57
Congenital Myopathy with Cleft Palate and Malignant Hyperthermia 75
Congenital Myopathy - Cleft Palate - Malignant Hyperthermia 53
Congenital Myopathy Cleft Palate and Malignant Hyperthermia 53

Characteristics:

Orphanet epidemiological data:

59
native american myopathy
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
native american myopathy:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Native American Myopathy

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 168572Disease definitionNative American myopathy (NAM) is a neuromuscular disorder characterized by weakness, arthrogryposis, kyphoscoliosis, short stature, cleft palate, ptosis and susceptibility to malignant hyperthermia during anesthesia.EpidemiologyNAM is reported exclusively in Native American Indians (Lumbee Indian population of North Carolina). Within this population, the prevalence of NAM is estimated at approximately 1:5,000.EtiologyThe NAM locus has been localized to 12q13.13-14.1.Genetic counselingThe disease is transmitted in an autosomal recessive manner.Visit the Orphanet disease page for more resources.

MalaCards based summary : Native American Myopathy, also known as congenital myopathy-cleft palate-malignant hyperthermia syndrome, is related to malignant hyperthermia and necrotizing autoimmune myopathy. An important gene associated with Native American Myopathy is STAC3 (SH3 And Cysteine Rich Domain 3), and among its related pathways/superpathways are Presenilin-Mediated Signaling and Netrin Signaling. Affiliated tissues include testes and skeletal muscle, and related phenotypes are cryptorchidism and cleft palate

OMIM : 57 Native American myopathy (NAM) is an autosomal recessive disorder characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia provoked by anesthesia. It was first reported in the Lumbee Indian tribe in North Carolina (summary by Stamm et al., 2008). (255995)

UniProtKB/Swiss-Prot : 75 Native American myopathy: A disease characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia provoked by anesthesia.

Disease Ontology : 12 A neuromuscular disease characterized by congenital weakness, arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kykphoscoliosis, talipes deformities and susceptibility to malignant hyperthermia provoked by anesthesia; that has material basis in homozygous mutation in the STAC3 gene on chromosome 12q13.

Related Diseases for Native American Myopathy

Graphical network of the top 20 diseases related to Native American Myopathy:



Diseases related to Native American Myopathy

Symptoms & Phenotypes for Native American Myopathy

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears

Growth Height:
short stature

Head And Neck Face:
micrognathia
myopathic facies
oral hypotonia

Neurologic Peripheral Nervous System:
hyporeflexia

Skeletal Spine:
kyphoscoliosis

Abdomen Gastrointestinal:
poor feeding

Neurologic Central Nervous System:
mental retardation (rare)
enlarged ventricles (in some)

Skeletal Feet:
talipes deformities

Head And Neck Eyes:
ptosis
telecanthus
downslanting palpebral fissures
short palpebral fissures

Head And Neck Mouth:
cleft palate
high-arched palate
downturned mouth

Genitourinary External Genitalia Male:
cryptorchidism

Metabolic Features:
malignant hyperthermia

Muscle Soft Tissue:
muscle wasting
muscle weakness, congenital

Skeletal:
joint contractures

Respiratory:
restrictive respiratory insufficiency

Laboratory Abnormalities:
serum creatine kinase may be increased
increased prevalence among the native american lumbee indians


Clinical features from OMIM:

255995

Human phenotypes related to Native American Myopathy:

32 (show all 25)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 32 HP:0000028
2 cleft palate 32 HP:0000175
3 high palate 32 HP:0000218
4 micrognathia 32 HP:0000347
5 low-set ears 32 HP:0000369
6 downslanted palpebral fissures 32 HP:0000494
7 telecanthus 32 HP:0000506
8 ptosis 32 HP:0000508
9 blepharophimosis 32 HP:0000581
10 intellectual disability 32 occasional (7.5%) HP:0001249
11 hyporeflexia 32 HP:0001265
12 muscle weakness 32 HP:0001324
13 flexion contracture 32 HP:0001371
14 talipes 32 HP:0001883
15 malignant hyperthermia 32 HP:0002047
16 myopathic facies 32 HP:0002058
17 restrictive deficit on pulmonary function testing 32 HP:0002111
18 ventriculomegaly 32 occasional (7.5%) HP:0002119
19 downturned corners of mouth 32 HP:0002714
20 kyphoscoliosis 32 HP:0002751
21 skeletal muscle atrophy 32 HP:0003202
22 short stature 32 HP:0004322
23 multiple skeletal anomalies 32 HP:0005775
24 feeding difficulties 32 HP:0011968
25 short palpebral fissure 32 HP:0012745

Drugs & Therapeutics for Native American Myopathy

Search Clinical Trials , NIH Clinical Center for Native American Myopathy

Cochrane evidence based reviews: native american myopathy

Genetic Tests for Native American Myopathy

Genetic tests related to Native American Myopathy:

# Genetic test Affiliating Genes
1 Native American Myopathy 29 STAC3

Anatomical Context for Native American Myopathy

MalaCards organs/tissues related to Native American Myopathy:

41
Testes, Skeletal Muscle

Publications for Native American Myopathy

Articles related to Native American Myopathy:

# Title Authors Year
1
Novel STAC3 Mutations in the First Non-Amerindian Patient with Native American Myopathy. ( 28411587 )
2017
2
Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy. ( 23736855 )
2013
3
Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia. ( 18553514 )
2008

Variations for Native American Myopathy

UniProtKB/Swiss-Prot genetic disease variations for Native American Myopathy:

75
# Symbol AA change Variation ID SNP ID
1 STAC3 p.Trp284Ser VAR_071313 rs140291094

ClinVar genetic disease variations for Native American Myopathy:

6
(show all 38)
# Gene Variation Type Significance SNP ID Assembly Location
1 STAC3 NM_145064.2(STAC3): c.851G> C (p.Trp284Ser) single nucleotide variant Pathogenic rs140291094 GRCh37 Chromosome 12, 57638105: 57638105
2 STAC3 NM_145064.2(STAC3): c.851G> C (p.Trp284Ser) single nucleotide variant Pathogenic rs140291094 GRCh38 Chromosome 12, 57244322: 57244322
3 STAC3 NM_145064.2(STAC3): c.1086G> A (p.Glu362=) single nucleotide variant Benign rs61739642 GRCh38 Chromosome 12, 57243821: 57243821
4 STAC3 NM_145064.2(STAC3): c.1086G> A (p.Glu362=) single nucleotide variant Benign rs61739642 GRCh37 Chromosome 12, 57637604: 57637604
5 STAC3 NM_145064.2(STAC3): c.1023G> C (p.Ala341=) single nucleotide variant Benign rs61747067 GRCh37 Chromosome 12, 57637667: 57637667
6 STAC3 NM_145064.2(STAC3): c.1023G> C (p.Ala341=) single nucleotide variant Benign rs61747067 GRCh38 Chromosome 12, 57243884: 57243884
7 STAC3 NM_145064.2(STAC3): c.842A> G (p.Asn281Ser) single nucleotide variant Benign rs115276341 GRCh37 Chromosome 12, 57638114: 57638114
8 STAC3 NM_145064.2(STAC3): c.842A> G (p.Asn281Ser) single nucleotide variant Benign rs115276341 GRCh38 Chromosome 12, 57244331: 57244331
9 STAC3 NM_145064.2(STAC3): c.604-8C> T single nucleotide variant Benign rs76823783 GRCh37 Chromosome 12, 57639002: 57639002
10 STAC3 NM_145064.2(STAC3): c.604-8C> T single nucleotide variant Benign rs76823783 GRCh38 Chromosome 12, 57245219: 57245219
11 STAC3 NM_145064.2(STAC3): c.570G> A (p.Lys190=) single nucleotide variant Benign rs76667525 GRCh38 Chromosome 12, 57246837: 57246837
12 STAC3 NM_145064.2(STAC3): c.570G> A (p.Lys190=) single nucleotide variant Benign rs76667525 GRCh37 Chromosome 12, 57640620: 57640620
13 STAC3 NM_145064.2(STAC3): c.355C> T (p.Arg119Cys) single nucleotide variant Benign rs146313451 GRCh38 Chromosome 12, 57248783: 57248783
14 STAC3 NM_145064.2(STAC3): c.355C> T (p.Arg119Cys) single nucleotide variant Benign rs146313451 GRCh37 Chromosome 12, 57642566: 57642566
15 STAC3 NM_145064.2(STAC3): c.487G> A (p.Ala163Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 57641927: 57641927
16 STAC3 NM_145064.2(STAC3): c.487G> A (p.Ala163Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 57248144: 57248144
17 STAC3 NM_145064.2(STAC3): c.157G> A (p.Val53Met) single nucleotide variant Uncertain significance rs141938531 GRCh37 Chromosome 12, 57643001: 57643001
18 STAC3 NM_145064.2(STAC3): c.157G> A (p.Val53Met) single nucleotide variant Uncertain significance rs141938531 GRCh38 Chromosome 12, 57249218: 57249218
19 STAC3 NM_145064.2(STAC3): c.932A> G (p.His311Arg) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 57637935: 57637935
20 STAC3 NM_145064.2(STAC3): c.932A> G (p.His311Arg) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 57244152: 57244152
21 STAC3 NM_145064.2(STAC3): c.383_399del17 (p.His128Leufs) deletion Uncertain significance GRCh37 Chromosome 12, 57642522: 57642538
22 STAC3 NM_145064.2(STAC3): c.383_399del17 (p.His128Leufs) deletion Uncertain significance GRCh38 Chromosome 12, 57248739: 57248755
23 STAC3 NM_001286256.1(STAC3): c.443T> A (p.Met148Lys) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 57640630: 57640630
24 STAC3 NM_001286256.1(STAC3): c.443T> A (p.Met148Lys) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 57246847: 57246847
25 STAC3 NM_145064.2(STAC3): c.883T> C (p.Phe295Leu) single nucleotide variant Likely benign rs138921555 GRCh37 Chromosome 12, 57637984: 57637984
26 STAC3 NM_145064.2(STAC3): c.883T> C (p.Phe295Leu) single nucleotide variant Likely benign rs138921555 GRCh38 Chromosome 12, 57244201: 57244201
27 STAC3 NM_145064.2(STAC3): c.259G> A (p.Asp87Asn) single nucleotide variant Uncertain significance rs776406787 GRCh38 Chromosome 12, 57249116: 57249116
28 STAC3 NM_145064.2(STAC3): c.259G> A (p.Asp87Asn) single nucleotide variant Uncertain significance rs776406787 GRCh37 Chromosome 12, 57642899: 57642899
29 STAC3 NM_145064.2(STAC3): c.251T> G (p.Leu84Arg) single nucleotide variant Uncertain significance rs201754072 GRCh38 Chromosome 12, 57249124: 57249124
30 STAC3 NM_145064.2(STAC3): c.251T> G (p.Leu84Arg) single nucleotide variant Uncertain significance rs201754072 GRCh37 Chromosome 12, 57642907: 57642907
31 STAC3 NM_145064.2(STAC3): c.207_212delGGAAGA (p.Glu75_Glu76del) deletion Uncertain significance GRCh38 Chromosome 12, 57249163: 57249168
32 STAC3 NM_145064.2(STAC3): c.207_212delGGAAGA (p.Glu75_Glu76del) deletion Uncertain significance GRCh37 Chromosome 12, 57642946: 57642951
33 STAC3 NM_145064.2(STAC3): c.987G> T (p.Lys329Asn) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 57244097: 57244097
34 STAC3 NM_145064.2(STAC3): c.987G> T (p.Lys329Asn) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 57637880: 57637880
35 STAC3 NM_145064.2(STAC3): c.249G> A (p.Lys83=) single nucleotide variant Likely benign GRCh38 Chromosome 12, 57249126: 57249126
36 STAC3 NM_145064.2(STAC3): c.249G> A (p.Lys83=) single nucleotide variant Likely benign GRCh37 Chromosome 12, 57642909: 57642909
37 STAC3 NM_145064.2(STAC3): c.221A> G (p.Glu74Gly) single nucleotide variant Uncertain significance rs199716296 GRCh37 Chromosome 12, 57642937: 57642937
38 STAC3 NM_145064.2(STAC3): c.221A> G (p.Glu74Gly) single nucleotide variant Uncertain significance rs199716296 GRCh38 Chromosome 12, 57249154: 57249154

Expression for Native American Myopathy

Search GEO for disease gene expression data for Native American Myopathy.

Pathways for Native American Myopathy

Pathways related to Native American Myopathy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.31 CACNA1S RYR1
2 10.65 CACNA1S RYR1
3 9.7 CACNA1S RYR1

GO Terms for Native American Myopathy

Cellular components related to Native American Myopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.8 CACNA1S QDPR RYR1 STAC STAC2 STAC3
2 voltage-gated calcium channel complex GO:0005891 9.26 CACNA1S STAC3
3 I band GO:0031674 9.16 CACNA1S RYR1
4 sarcolemma GO:0042383 9.13 CACNA1S RYR1 STAC3
5 T-tubule GO:0030315 8.8 CACNA1S RYR1 STAC

Biological processes related to Native American Myopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 intracellular signal transduction GO:0035556 9.5 STAC STAC2 STAC3
2 calcium ion transport GO:0006816 9.4 CACNA1S RYR1
3 calcium ion transmembrane transport GO:0070588 9.37 CACNA1S RYR1
4 positive regulation of protein localization to plasma membrane GO:1903078 9.26 STAC STAC3
5 skeletal muscle fiber development GO:0048741 9.16 RYR1 STAC3
6 muscle contraction GO:0006936 9.13 CACNA1S RYR1 STAC
7 cellular response to caffeine GO:0071313 8.62 CACNA1S RYR1

Molecular functions related to Native American Myopathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.55 CACNA1S RYR1 STAC STAC2 STAC3
2 calcium channel activity GO:0005262 8.96 CACNA1S RYR1
3 voltage-gated calcium channel activity GO:0005245 8.62 CACNA1S RYR1

Sources for Native American Myopathy

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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