MCID: CHR660
MIFTS: 28

Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a:

Name: Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a 57
Cmt2a2 57 59 75
Charcot-Marie-Tooth Disease, Axonal, Type 2a2a 57 29
Charcot-Marie-Tooth Disease, Axonal, Type 2a2 57 73
Hereditary Motor and Sensory Neuropathy Iia2 57 75
Charcot-Marie-Tooth Disease, Type 2a2a 29 6
Hmsn Iia2 57 75
Cmt2a2a 57 75
Hmsn2a2 57 75
Autosomal Dominant Charcot-Marie-Tooth Disease Type 2a2 59
Charcot-Marie-Tooth Disease, Axonal, Type 2a2; Cmt2a2 57
Hereditary Motor and Sensory Neuropathy Iia2; Hmsn2a2 57
Charcot-Marie-Tooth Disease, Neuronal, Type 2a2 57
Charcot-Marie-Tooth Disease Neuronal Type 2a2 75
Charcot-Marie-Tooth Disease Axonal Type 2a2 75
Charcot-Marie-Tooth Neuropathy, Type 2a2 57
Charcot-Marie-Tooth Neuropathy Type 2a2 75
Charcot-Marie-Tooth Disease 2a2a 75

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant charcot-marie-tooth disease type 2a2
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable severity
slowly progressive
variable age at onset (childhood to age 50)
earlier onset is associated with a more severe disorder
usually begins in feet and legs (peroneal distribution), but may progress to upper limbs
one family with a fatal subacute encephalopathy has been reported
up to 25% of patients are asymptomatic or mildly affected, suggesting incomplete penetrance


HPO:

32
charcot-marie-tooth disease, axonal, autosomal dominant, type 2a2a:
Onset and clinical course variable expressivity incomplete penetrance slow progression
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

OMIM : 57 Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a slow motor median nerve conduction velocity (NCV) (less than 38 m/s), and type 2, the axonal form, with a normal or slightly reduced NCV. Distal hereditary motor neuropathy (dHMN), also known as spinal CMT, is a third type of CMT characterized by normal motor and sensory NCV and degeneration of spinal cord anterior horn cells. See CMT1B (118200) and CMT1A (118220) for descriptions of autosomal dominant slow nerve conduction types of Charcot-Marie-Tooth disease. See CMT4A (214400) and CMTX1 (302800) for autosomal recessive and X-linked forms of Charcot-Marie-Tooth disease, respectively. For a discussion of genetic heterogeneity of CMT type 2, see 118210. (609260)

MalaCards based summary : Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a, also known as cmt2a2, is related to charcot-marie-tooth disease type 2a2, and has symptoms including pain An important gene associated with Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a is MFN2 (Mitofusin 2). Affiliated tissues include spinal cord, and related phenotypes are hearing impairment and optic atrophy

UniProtKB/Swiss-Prot : 75 Charcot-Marie-Tooth disease 2A2A: An axonal 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). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.

Related Diseases for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

Symptoms via clinical synopsis from OMIM:

57
Skeletal Feet:
pes cavus
foot deformities
hammer toes

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal sensory impairment
distal limb muscle weakness due to peripheral neuropathy
distal limb muscle atrophy due to peripheral neuropathy
more
Head And Neck Ears:
hearing loss (uncommon)

Skeletal Spine:
scoliosis (in those with early onset)

Neurologic Central Nervous System:
pain
cognitive decline (1 family)
spasticity (1 family)
pyramidal features (rare)
tremor (rare)
more
Head And Neck Eyes:
optic atrophy (uncommon)

Skeletal:
contractures (in those with early onset)


Clinical features from OMIM:

609260

Human phenotypes related to Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a:

32 (show all 26)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 32 occasional (7.5%) HP:0000365
2 optic atrophy 32 occasional (7.5%) HP:0000648
3 spasticity 32 occasional (7.5%) HP:0001257
4 hyporeflexia 32 HP:0001265
5 mental deterioration 32 occasional (7.5%) HP:0001268
6 hypertonia 32 HP:0001276
7 areflexia 32 HP:0001284
8 tremor 32 occasional (7.5%) HP:0001337
9 hyperreflexia 32 occasional (7.5%) HP:0001347
10 flexion contracture 32 HP:0001371
11 pes cavus 32 HP:0001761
12 hammertoe 32 HP:0001765
13 distal muscle weakness 32 HP:0002460
14 scoliosis 32 HP:0002650
15 distal sensory impairment 32 HP:0002936
16 steppage gait 32 HP:0003376
17 axonal degeneration/regeneration 32 HP:0003378
18 decreased number of peripheral myelinated nerve fibers 32 HP:0003380
19 onion bulb formation 32 HP:0003383
20 peripheral axonal atrophy 32 HP:0003384
21 decreased motor nerve conduction velocity 32 HP:0003431
22 babinski sign 32 HP:0003487
23 limb muscle weakness 32 HP:0003690
24 distal amyotrophy 32 HP:0003693
25 foot dorsiflexor weakness 32 HP:0009027
26 pain 32 HP:0012531

UMLS symptoms related to Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a:


pain

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a

Genetic Tests for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

Genetic tests related to Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Type 2a2a 29 MFN2
2 Charcot-Marie-Tooth Disease, Axonal, Type 2a2a 29

Anatomical Context for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a:

41
Spinal Cord

Publications for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

Variations for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a:

75 (show all 11)
# Symbol AA change Variation ID SNP ID
1 MFN2 p.Val69Phe VAR_018607 rs28940296
2 MFN2 p.Leu76Pro VAR_018608 rs28940293
3 MFN2 p.Arg94Gln VAR_018609 rs28940291
4 MFN2 p.Pro251Ala VAR_018610 rs28940295
5 MFN2 p.Arg280His VAR_018611 rs28940294
6 MFN2 p.Trp740Ser VAR_018612 rs28940292
7 MFN2 p.Lys357Asn VAR_022464 rs119103261
8 MFN2 p.Arg364Trp VAR_029880 rs119103265
9 MFN2 p.Leu233Val VAR_067088
10 MFN2 p.Glu744Met VAR_067089
11 MFN2 p.Arg707Trp VAR_078443 rs119103267

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type 2a2a:

6
(show top 50) (show all 60)
# Gene Variation Type Significance SNP ID Assembly Location
1 MFN2 NM_014874.3(MFN2): c.281G> A (p.Arg94Gln) single nucleotide variant Pathogenic rs28940291 GRCh37 Chromosome 1, 12052717: 12052717
2 MFN2 NM_014874.3(MFN2): c.281G> A (p.Arg94Gln) single nucleotide variant Pathogenic rs28940291 GRCh38 Chromosome 1, 11992660: 11992660
3 MFN2 NM_014874.3(MFN2): c.2219G> C (p.Trp740Ser) single nucleotide variant Pathogenic rs28940292 GRCh37 Chromosome 1, 12071567: 12071567
4 MFN2 NM_014874.3(MFN2): c.2219G> C (p.Trp740Ser) single nucleotide variant Pathogenic rs28940292 GRCh38 Chromosome 1, 12011510: 12011510
5 MFN2 NM_014874.3(MFN2): c.227T> C (p.Leu76Pro) single nucleotide variant Pathogenic rs28940293 GRCh37 Chromosome 1, 12052663: 12052663
6 MFN2 NM_014874.3(MFN2): c.227T> C (p.Leu76Pro) single nucleotide variant Pathogenic rs28940293 GRCh38 Chromosome 1, 11992606: 11992606
7 MFN2 NM_014874.3(MFN2): c.839G> A (p.Arg280His) single nucleotide variant Pathogenic rs28940294 GRCh37 Chromosome 1, 12061480: 12061480
8 MFN2 NM_014874.3(MFN2): c.839G> A (p.Arg280His) single nucleotide variant Pathogenic rs28940294 GRCh38 Chromosome 1, 12001423: 12001423
9 MFN2 NM_014874.3(MFN2): c.751C> G (p.Pro251Ala) single nucleotide variant Pathogenic rs28940295 GRCh37 Chromosome 1, 12059087: 12059087
10 MFN2 NM_014874.3(MFN2): c.751C> G (p.Pro251Ala) single nucleotide variant Pathogenic rs28940295 GRCh38 Chromosome 1, 11999030: 11999030
11 MFN2 NM_014874.3(MFN2): c.205G> T (p.Val69Phe) single nucleotide variant Pathogenic rs28940296 GRCh37 Chromosome 1, 12052641: 12052641
12 MFN2 NM_014874.3(MFN2): c.205G> T (p.Val69Phe) single nucleotide variant Pathogenic rs28940296 GRCh38 Chromosome 1, 11992584: 11992584
13 MFN2 NM_014874.3(MFN2): c.1071G> C (p.Lys357Asn) single nucleotide variant Likely pathogenic rs119103261 GRCh37 Chromosome 1, 12062071: 12062071
14 MFN2 NM_014874.3(MFN2): c.1071G> C (p.Lys357Asn) single nucleotide variant Likely pathogenic rs119103261 GRCh38 Chromosome 1, 12002014: 12002014
15 MFN2 NM_014874.3(MFN2): c.493C> G (p.His165Asp) single nucleotide variant Pathogenic rs119103262 GRCh37 Chromosome 1, 12057372: 12057372
16 MFN2 NM_014874.3(MFN2): c.493C> G (p.His165Asp) single nucleotide variant Pathogenic rs119103262 GRCh38 Chromosome 1, 11997315: 11997315
17 MFN2 NM_014874.3(MFN2): c.280C> T (p.Arg94Trp) single nucleotide variant Pathogenic rs119103263 GRCh37 Chromosome 1, 12052716: 12052716
18 MFN2 NM_014874.3(MFN2): c.280C> T (p.Arg94Trp) single nucleotide variant Pathogenic rs119103263 GRCh38 Chromosome 1, 11992659: 11992659
19 MFN2 NM_014874.3(MFN2): c.1090C> T (p.Arg364Trp) single nucleotide variant Pathogenic rs119103265 GRCh37 Chromosome 1, 12062090: 12062090
20 MFN2 NM_014874.3(MFN2): c.1090C> T (p.Arg364Trp) single nucleotide variant Pathogenic rs119103265 GRCh38 Chromosome 1, 12002033: 12002033
21 MFN2 NM_014874.3(MFN2): c.2119C> T (p.Arg707Trp) single nucleotide variant Pathogenic/Likely pathogenic rs119103267 GRCh37 Chromosome 1, 12069698: 12069698
22 MFN2 NM_014874.3(MFN2): c.2119C> T (p.Arg707Trp) single nucleotide variant Pathogenic/Likely pathogenic rs119103267 GRCh38 Chromosome 1, 12009641: 12009641
23 MFN2 NM_014874.3(MFN2): c.310C> T (p.Arg104Trp) single nucleotide variant Pathogenic rs119103268 GRCh37 Chromosome 1, 12052746: 12052746
24 MFN2 NM_014874.3(MFN2): c.310C> T (p.Arg104Trp) single nucleotide variant Pathogenic rs119103268 GRCh38 Chromosome 1, 11992689: 11992689
25 MFN2 NM_014874.3(MFN2): c.1392+2T> C single nucleotide variant Pathogenic rs111723244 GRCh37 Chromosome 1, 12064672: 12064672
26 MFN2 NM_014874.3(MFN2): c.1392+2T> C single nucleotide variant Pathogenic rs111723244 GRCh38 Chromosome 1, 12004615: 12004615
27 MFN2 NM_014874.3(MFN2): c.1085C> T (p.Thr362Met) single nucleotide variant Pathogenic rs387906991 GRCh37 Chromosome 1, 12062085: 12062085
28 MFN2 NM_014874.3(MFN2): c.1085C> T (p.Thr362Met) single nucleotide variant Pathogenic rs387906991 GRCh38 Chromosome 1, 12002028: 12002028
29 MFN2 NM_001127660.1(MFN2): c.775C> T (p.Arg259Cys) single nucleotide variant Pathogenic/Likely pathogenic rs587777875 GRCh37 Chromosome 1, 12059111: 12059111
30 MFN2 NM_001127660.1(MFN2): c.775C> T (p.Arg259Cys) single nucleotide variant Pathogenic/Likely pathogenic rs587777875 GRCh38 Chromosome 1, 11999054: 11999054
31 MFN2 NM_014874.3(MFN2): c.1148C> T (p.Ala383Val) single nucleotide variant Pathogenic rs794727035 GRCh37 Chromosome 1, 12062148: 12062148
32 MFN2 NM_014874.3(MFN2): c.1148C> T (p.Ala383Val) single nucleotide variant Pathogenic rs794727035 GRCh38 Chromosome 1, 12002091: 12002091
33 MFN2 NM_001127660.1(MFN2): c.746C> T (p.Ser249Phe) single nucleotide variant Pathogenic rs794729198 GRCh38 Chromosome 1, 11999025: 11999025
34 MFN2 NM_001127660.1(MFN2): c.746C> T (p.Ser249Phe) single nucleotide variant Pathogenic rs794729198 GRCh37 Chromosome 1, 12059082: 12059082
35 MFN2 NM_014874.3(MFN2): c.436C> T (p.Leu146Phe) single nucleotide variant Likely pathogenic rs863224969 GRCh37 Chromosome 1, 12056337: 12056337
36 MFN2 NM_014874.3(MFN2): c.436C> T (p.Leu146Phe) single nucleotide variant Likely pathogenic rs863224969 GRCh38 Chromosome 1, 11996280: 11996280
37 MFN2 NM_014874.3(MFN2): c.494A> G (p.His165Arg) single nucleotide variant Pathogenic rs863224970 GRCh38 Chromosome 1, 11997316: 11997316
38 MFN2 NM_014874.3(MFN2): c.494A> G (p.His165Arg) single nucleotide variant Pathogenic rs863224970 GRCh37 Chromosome 1, 12057373: 12057373
39 MFN2 NM_014874.3(MFN2): c.707C> T (p.Thr236Met) single nucleotide variant Pathogenic/Likely pathogenic rs773159585 GRCh37 Chromosome 1, 12058934: 12058934
40 MFN2 NM_014874.3(MFN2): c.707C> T (p.Thr236Met) single nucleotide variant Pathogenic/Likely pathogenic rs773159585 GRCh38 Chromosome 1, 11998877: 11998877
41 MFN2 NM_014874.3(MFN2): c.1126A> G (p.Met376Val) single nucleotide variant Likely pathogenic rs863224967 GRCh38 Chromosome 1, 12002069: 12002069
42 MFN2 NM_014874.3(MFN2): c.1126A> G (p.Met376Val) single nucleotide variant Likely pathogenic rs863224967 GRCh37 Chromosome 1, 12062126: 12062126
43 MFN2 NM_014874.3(MFN2): c.2256C> A (p.Tyr752Ter) single nucleotide variant Pathogenic rs863224968 GRCh37 Chromosome 1, 12071604: 12071604
44 MFN2 NM_014874.3(MFN2): c.2256C> A (p.Tyr752Ter) single nucleotide variant Pathogenic rs863224968 GRCh38 Chromosome 1, 12011547: 12011547
45 MFN2 NM_001127660.1(MFN2): c.730G> T (p.Val244Leu) single nucleotide variant Pathogenic rs879253777 GRCh37 Chromosome 1, 12059066: 12059066
46 MFN2 NM_001127660.1(MFN2): c.730G> T (p.Val244Leu) single nucleotide variant Pathogenic rs879253777 GRCh38 Chromosome 1, 11999009: 11999009
47 MFN2 NM_001127660.1(MFN2): c.479T> G (p.Val160Gly) single nucleotide variant Likely pathogenic rs879253861 GRCh37 Chromosome 1, 12057358: 12057358
48 MFN2 NM_001127660.1(MFN2): c.479T> G (p.Val160Gly) single nucleotide variant Likely pathogenic rs879253861 GRCh38 Chromosome 1, 11997301: 11997301
49 MFN2 NM_001127660.1(MFN2): c.526G> A (p.Gly176Ser) single nucleotide variant Likely pathogenic rs879253862 GRCh37 Chromosome 1, 12057405: 12057405
50 MFN2 NM_001127660.1(MFN2): c.526G> A (p.Gly176Ser) single nucleotide variant Likely pathogenic rs879253862 GRCh38 Chromosome 1, 11997348: 11997348

Expression for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

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GO Terms for Charcot-Marie-Tooth Disease, Axonal, Autosomal Dominant, Type...

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