CMT1D
MCID: CHR653
MIFTS: 39

Charcot-Marie-Tooth Disease, Demyelinating, Type 1d (CMT1D)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:

Name: Charcot-Marie-Tooth Disease, Demyelinating, Type 1d 57 20 29 6
Charcot-Marie-Tooth Disease Type 1d 12 20 58 15
Cmt1d 57 12 58 73
Hereditary Motor and Sensory Neuropathy 1d 57 12 20
Charcot-Marie-Tooth Disease, Type 1d 57 13 71
Hmsn Id 57 12 73
Hmsn1d 57 12 73
Charcot-Marie-Tooth Neuropathy Type 1d 12 73
Charcot-Marie-Tooth Disease Demyelinating Type 1d 73
Hereditary Motor and Sensory Neuropathy Id 73
Charcot-Marie-Tooth Neuropathy, Type 1d 57
Charcot-Marie-Tooth Disease, Type Id 39
Charcot Marie Tooth Disease Type 1d 20
Charcot-Marie-Tooth Disease 1d 73
Hmsn 1d 20
Cmt 1d 20

Characteristics:

Orphanet epidemiological data:

58
charcot-marie-tooth disease type 1d
Inheritance: Autosomal dominant; Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: normal life expectancy;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
onset in first or second decade
usually begins in feet and legs (peroneal distribution)
upper limb involvement may occur later
genetic heterogeneity (see cmt1b, )
allelic disorders with overlapping phenotypes include congenital hypomyelinating neuropathy (chn, ) and dejerine-sottas syndrome (dss, )


HPO:

31
charcot-marie-tooth disease, demyelinating, type 1d:
Inheritance autosomal dominant inheritance heterogeneous
Onset and clinical course variable expressivity juvenile onset


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110150
OMIM® 57 607678
OMIM Phenotypic Series 57 PS118220
ICD10 32 G60.0
MESH via Orphanet 45 C537985
ICD10 via Orphanet 33 G60.0
UMLS via Orphanet 72 C1843247
Orphanet 58 ORPHA101084
MedGen 41 C1843247
UMLS 71 C1843247

Summaries for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

UniProtKB/Swiss-Prot : 73 Charcot-Marie-Tooth disease 1D: A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.

MalaCards based summary : Charcot-Marie-Tooth Disease, Demyelinating, Type 1d, also known as charcot-marie-tooth disease type 1d, is related to charcot-marie-tooth disease and deafness and charcot-marie-tooth disease. An important gene associated with Charcot-Marie-Tooth Disease, Demyelinating, Type 1d is EGR2 (Early Growth Response 2), and among its related pathways/superpathways is Neural Crest Differentiation. Related phenotypes are peripheral neuropathy and decreased motor nerve conduction velocity

Disease Ontology : 12 A Charcot-Marie-Tooth disease type 1 that has material basis in mutation in the early growth response gene-2 (EGR2).

OMIM® : 57 For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant Charcot-Marie-Tooth disease type 1, see CMT1B (118200). (607678) (Updated 05-Mar-2021)

Related Diseases for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Diseases in the Charcot-Marie-Tooth Disease, Demyelinating, Type 1b family:

Charcot-Marie-Tooth Disease, Demyelinating, Type 1a Charcot-Marie-Tooth Disease, Demyelinating, Type 1c
Charcot-Marie-Tooth Disease, Demyelinating, Type 1d Charcot-Marie-Tooth Disease, Demyelinating, Type 1f
Charcot-Marie-Tooth Disease, Demyelinating, Type 4f Charcot-Marie-Tooth Disease, Demyelinating, Type 1g

Diseases related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 76)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth disease and deafness 28.7 PRX PMP22 PMP2 NDRG1 MTMR2 MPZ
2 charcot-marie-tooth disease 27.8 PRX PMP22 PMP2 NDRG1 MTMR2 MPZ
3 tooth disease 27.8 PRX PMP22 PMP2 NDRG1 MTMR2 MPZ
4 foot drop 10.2 PMP22 MPZ
5 charcot-marie-tooth disease, axonal, type 2a1 10.2 MPZ GDAP1
6 slowed nerve conduction velocity, autosomal dominant 10.2 MPZ GJB1
7 charcot-marie-tooth disease type 5 10.2 PRX GARS1
8 amyotrophic neuralgia 10.2 PMP22 MPZ
9 roussy-levy hereditary areflexic dystasia 10.2 PMP22 MPZ
10 charcot-marie-tooth disease x-linked recessive 4 10.1 MPZ GJB1
11 spinal muscular atrophy with lower extremity predominance 10.1 GDAP1 GARS1
12 mononeuropathy 10.1 PMP22 MPZ
13 charcot-marie-tooth disease, axonal, type 2n 10.1 GDAP1 GARS1
14 pupil disease 10.1 MPZ GDAP1 EGR2
15 argyll robertson pupil 10.1 MPZ GDAP1 EGR2
16 abnormal pupillary function 10.1 MPZ GDAP1 EGR2
17 polyradiculoneuropathy 10.1 PMP22 MPZ
18 autoimmune neuropathy 10.1 PMP2 MPZ
19 chronic inflammatory demyelinating polyradiculoneuropathy 10.1 PMP22 MPZ
20 charcot-marie-tooth disease, axonal, type 2w 10.1 MPZ GJB1 GDAP1
21 charcot-marie-tooth disease, axonal, type 2p 10.0 LITAF GDAP1
22 brachial plexus neuropathy 10.0 PMP22 MPZ GJB1
23 charcot-marie-tooth disease, axonal, type 2l 10.0 MPZ GDAP1 GARS1
24 distal hereditary motor neuronopathy type 2 10.0 MPZ GARS1
25 nerve compression syndrome 10.0 PMP22 MPZ GJB1
26 charcot-marie-tooth disease, axonal, type 2b2 10.0 MPZ GDAP1 GARS1
27 waardenburg syndrome, type 4a 10.0 MPZ GJB1
28 neuropathy, hereditary motor and sensory, russe type 10.0 NDRG1 GDAP1 EGR2
29 axonal neuropathy 10.0 PMP22 GDAP1 GARS1
30 cortical dysplasia, complex, with other brain malformations 6 10.0 PMP22 LITAF GDAP1
31 yunis-varon syndrome 9.9 MTMR2 GDAP1
32 guillain-barre syndrome 9.9 PMP22 PMP2 MPZ
33 autoimmune peripheral neuropathy 9.9 PMP2 MPZ GJB1
34 charcot-marie-tooth disease, dominant intermediate e 9.9 MTMR2 MPZ GDAP1
35 neuronopathy, distal hereditary motor, type va 9.9 GDAP1 GARS1
36 charcot-marie-tooth disease, dominant intermediate a 9.9 PRX MPZ GJB1 GDAP1
37 neuritis 9.9 PMP22 PMP2 MPZ
38 motor peripheral neuropathy 9.9 PMP22 LITAF GARS1
39 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 9.9 PMP22 MPZ GJB1 EGR2
40 spinal muscular atrophy 9.9 PMP22 LITAF GARS1
41 carpal tunnel syndrome 9.9 PMP22 MPZ
42 charcot-marie-tooth disease, x-linked recessive, 2 9.8 MPZ LITAF GJB1 EGR2
43 charcot-marie-tooth disease, dominant intermediate c 9.8 MPZ GJB1 GDAP1 GARS1
44 hereditary motor and sensory neuropathy, type iic 9.8 MPZ GJB1 GDAP1 GARS1
45 charcot-marie-tooth disease, type 4h 9.8 PRX MTMR2 MPZ GDAP1
46 charcot-marie-tooth disease, type 4b3 9.7 PMP22 MTMR2 MPZ GDAP1
47 charcot-marie-tooth disease, axonal, type 2i 9.7 PRX MPZ GJB1 GDAP1 GARS1
48 charcot-marie-tooth disease, dominant intermediate b 9.7 MTMR2 MPZ LITAF GDAP1
49 charcot-marie-tooth disease, axonal, type 2d 9.7 PMP22 MPZ GJB1 GDAP1 GARS1
50 charcot-marie-tooth disease, axonal, type 2j 9.6 PRX MTMR2 MPZ GDAP1 EGR2

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:



Diseases related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Human phenotypes related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 peripheral neuropathy 31 HP:0009830
2 decreased motor nerve conduction velocity 31 HP:0003431
3 steppage gait 31 HP:0003376
4 distal amyotrophy 31 HP:0003693
5 distal muscle weakness 31 HP:0002460
6 upper limb muscle weakness 31 HP:0003484
7 foot dorsiflexor weakness 31 HP:0009027

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Peripheral Nervous System:
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
'steppage' gait
foot drop
decreased motor nerve conduction velocity (ncv) (less than 38 m/s)

Clinical features from OMIM®:

607678 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.65 EGR2 GARS1 GDAP1 GJB1 MPZ MTMR2
2 nervous system MP:0003631 9.36 EGR2 GARS1 GDAP1 GJB1 LITAF MPZ

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Genetic Tests for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Genetic tests related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Demyelinating, Type 1d 29 EGR2

Anatomical Context for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Publications for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Articles related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:

# Title Authors PMID Year
1
Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C. 6 57
12525712 2003
2
Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth disease family. 6
15947997 2005
3
EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy. 6
11523566 2001
4
Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies. 6
10369870 1999
5
Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. 57
9537424 1998
6
A novel family with axonal Charcot-Marie-Tooth disease caused by a mutation in the EGR2 gene. 61
30843326 2019
7
Development and validation of the Charcot-Marie-Tooth Disease Infant Scale. 61
30476010 2018
8
Genetic evaluation of inherited motor/sensory neuropathy. 61
16106622 2004
9
A novel type of hereditary motor and sensory neuropathy characterized by a mild phenotype. 61
10520946 1999
10
Charcot-Marie-Tooth Neuropathy Type 1 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY 61
20301384 1998

Variations for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:

6 (show all 35)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 EGR2 NM_000399.5(EGR2):c.1225C>T (p.Arg409Trp) SNV Pathogenic 16750 rs104894159 10:64573173-64573173 10:62813413-62813413
2 EGR2 NM_000399.5(EGR2):c.1075C>T (p.Arg359Trp) SNV Pathogenic 16752 rs104894161 10:64573323-64573323 10:62813563-62813563
3 EGR2 NM_000399.5(EGR2):c.1076G>A (p.Arg359Gln) SNV Pathogenic 41007 rs281865136 10:64573322-64573322 10:62813562-62813562
4 EGR2 NM_000399.5(EGR2):c.1142G>A (p.Arg381His) SNV Pathogenic 41008 rs281865137 10:64573256-64573256 10:62813496-62813496
5 EGR2 NM_000399.5(EGR2):c.1160C>A (p.Thr387Asn) SNV Pathogenic 41009 rs281865139 10:64573238-64573238 10:62813478-62813478
6 EGR2 NM_000399.5(EGR2):c.*646C>T SNV Uncertain significance 300269 rs555024997 10:64572321-64572321 10:62812561-62812561
7 EGR2 NM_000399.5(EGR2):c.*456G>A SNV Uncertain significance 300270 rs886047090 10:64572511-64572511 10:62812751-62812751
8 EGR2 NM_000399.5(EGR2):c.918C>T (p.Ala306=) SNV Uncertain significance 300277 rs886047094 10:64573480-64573480 10:62813720-62813720
9 EGR2 NM_000399.5(EGR2):c.1084C>T (p.Arg362Ter) SNV Uncertain significance 548617 rs1554853028 10:64573314-64573314 10:62813554-62813554
10 EGR2 NM_000399.5(EGR2):c.924C>T (p.Ala308=) SNV Uncertain significance 300276 rs886047093 10:64573474-64573474 10:62813714-62813714
11 EGR2 NM_000399.5(EGR2):c.1360T>G (p.Cys454Gly) SNV Uncertain significance 300275 rs886047092 10:64573038-64573038 10:62813278-62813278
12 EGR2 NM_000399.5(EGR2):c.541C>T (p.Leu181Phe) SNV Uncertain significance 300278 rs886047095 10:64573857-64573857 10:62814097-62814097
13 EGR2 NM_000399.5(EGR2):c.*919G>C SNV Uncertain significance 300265 rs886047087 10:64572048-64572048 10:62812288-62812288
14 EGR2 NM_000399.5(EGR2):c.*655G>A SNV Uncertain significance 300268 rs886047089 10:64572312-64572312 10:62812552-62812552
15 EGR2 NM_000399.5(EGR2):c.*145T>A SNV Uncertain significance 300274 rs886047091 10:64572822-64572822 10:62813062-62813062
16 EGR2 NM_000399.5(EGR2):c.-64A>C SNV Uncertain significance 877688 10:64575853-64575853 10:62816093-62816093
17 EGR2 NM_000399.5(EGR2):c.-299G>A SNV Uncertain significance 877689 10:64576088-64576088 10:62816328-62816328
18 EGR2 NM_000399.5(EGR2):c.*618T>C SNV Uncertain significance 878661 10:64572349-64572349 10:62812589-62812589
19 EGR2 NM_000399.5(EGR2):c.*230G>T SNV Uncertain significance 878662 10:64572737-64572737 10:62812977-62812977
20 EGR2 NM_000399.5(EGR2):c.*150A>G SNV Uncertain significance 878663 10:64572817-64572817 10:62813057-62813057
21 EGR2 NM_000399.5(EGR2):c.*79C>A SNV Uncertain significance 879262 10:64572888-64572888 10:62813128-62813128
22 EGR2 NM_000399.5(EGR2):c.380C>T (p.Pro127Leu) SNV Uncertain significance 638513 rs932803146 10:64574018-64574018 10:62814258-62814258
23 EGR2 NM_000399.5(EGR2):c.644C>T (p.Thr215Met) SNV Likely benign 246013 rs139147487 10:64573754-64573754 10:62813994-62813994
24 EGR2 NM_000399.5(EGR2):c.246C>G (p.Val82=) SNV Likely benign 300279 rs144217451 10:64574152-64574152 10:62814392-62814392
25 EGR2 NM_000399.5(EGR2):c.192G>C (p.Met64Ile) SNV Likely benign 246186 rs146631014 10:64574206-64574206 10:62814446-62814446
26 EGR2 NM_000399.5(EGR2):c.174C>T (p.Gly58=) SNV Likely benign 246185 rs143793213 10:64574224-64574224 10:62814464-62814464
27 EGR2 NM_000399.5(EGR2):c.457A>C (p.Thr153Pro) SNV Likely benign 462785 rs202183386 10:64573941-64573941 10:62814181-62814181
28 EGR2 NM_000399.5(EGR2):c.-1A>G SNV Likely benign 300281 rs553201646 10:64575790-64575790 10:62816030-62816030
29 EGR2 NM_000399.5(EGR2):c.1352G>T (p.Gly451Val) SNV Benign/Likely benign 219918 rs138967272 10:64573046-64573046 10:62813286-62813286
30 EGR2 NM_000399.5(EGR2):c.1086A>C (p.Arg362=) SNV Benign 256013 rs45602133 10:64573312-64573312 10:62813552-62813552
31 EGR2 NM_000399.5(EGR2):c.*429G>A SNV Benign 300271 rs114237833 10:64572538-64572538 10:62812778-62812778
32 EGR2 NM_000399.5(EGR2):c.169+10G>T SNV Benign 300280 rs114201658 10:64575611-64575611 10:62815851-62815851
33 EGR2 NM_000399.5(EGR2):c.*874A>G SNV Benign 300266 rs61865882 10:64572093-64572093 10:62812333-62812333
34 EGR2 NM_000399.5(EGR2):c.*288G>A SNV Benign 300272 rs117395928 10:64572679-64572679 10:62812919-62812919
35 EGR2 NM_000399.5(EGR2):c.*287T>A SNV Benign 300273 rs61865883 10:64572680-64572680 10:62812920-62812920

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d:

73
# Symbol AA change Variation ID SNP ID
1 EGR2 p.Asp355Val VAR_007736
2 EGR2 p.Arg409Trp VAR_007738 rs104894159
3 EGR2 p.Arg359Trp VAR_009874 rs104894161
4 EGR2 p.Arg381His VAR_009875 rs281865137
5 EGR2 p.Arg381Cys VAR_029958
6 EGR2 p.Asp383Tyr VAR_029959 rs104894160
7 EGR2 p.Glu412Gly VAR_083345 rs749558026

Expression for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d.

Pathways for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Pathways related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.81 PMP22 MPZ GJB1

GO Terms for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

Cellular components related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 myelin sheath GO:0043209 8.62 PMP2 MPZ

Biological processes related to Charcot-Marie-Tooth Disease, Demyelinating, Type 1d according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 myelination GO:0042552 9.26 MPZ EGR2
2 peripheral nervous system development GO:0007422 9.16 PMP22 EGR2
3 myelin assembly GO:0032288 8.96 PMP22 MTMR2
4 peripheral nervous system myelin maintenance GO:0032287 8.62 PRX NDRG1

Sources for Charcot-Marie-Tooth Disease, Demyelinating, Type 1d

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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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