CMT4F
MCID: CHR670
MIFTS: 37

Charcot-Marie-Tooth Disease, Demyelinating, Type 4f (CMT4F)

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

Aliases & Classifications for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

Name: Charcot-Marie-Tooth Disease, Demyelinating, Type 4f 57 29 6 72
Charcot-Marie-Tooth Disease Type 4f 12 53 59 15
Cmt4f 57 12 59 74
Charcot-Marie-Tooth Disease, Type 4f 57 13 40
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4f 74
Charcot-Marie-Tooth Neuropathy Type 4f 74
Charcot-Marie-Tooth Disease 4f 74
Dejerine-Sottas Disease 72

Characteristics:

Orphanet epidemiological data:

59
charcot-marie-tooth disease type 4f
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
variable age at onset (range from early childhood to mid-adult)


HPO:

32
charcot-marie-tooth disease, demyelinating, type 4f:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0110193
ICD10 33 G60.0
ICD10 via Orphanet 34 G60.0
Orphanet 59 ORPHA99952
UMLS 72 C0011195 C3540453

Summaries for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

UniProtKB/Swiss-Prot : 74 Charcot-Marie-Tooth disease 4F: A recessive 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. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4F is characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome.

MalaCards based summary : Charcot-Marie-Tooth Disease, Demyelinating, Type 4f, also known as charcot-marie-tooth disease type 4f, is related to hypertrophic neuropathy of dejerine-sottas and peripheral nervous system disease, and has symptoms including ataxia, sensory An important gene associated with Charcot-Marie-Tooth Disease, Demyelinating, Type 4f is PRX (Periaxin). Affiliated tissues include skeletal muscle, and related phenotypes are vocal cord paresis and sensory ataxia

OMIM : 57 Charcot-Marie-Tooth disease type 4F is an autosomal recessive demyelinating neuropathy characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. Nerve conduction velocities are decreased and sural nerve biopsy shows loss of myelinated fibers. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome (DSS; 145900). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400). (614895)

Related Diseases for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

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

Charcot-Marie-Tooth Disease, Demyelinating, Type 1b 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 4f via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)
# Related Disease Score Top Affiliating Genes
1 hypertrophic neuropathy of dejerine-sottas 32.0 PRX MTMR2 GDAP1 DRP2
2 peripheral nervous system disease 29.8 PRX MTMR2 GDAP1
3 tooth disease 29.2 SBF2 PRX MTMR2 GDAP1
4 neuropathy 28.7 TDP1 SBF2 PRX GDAP1
5 charcot-marie-tooth disease 28.6 SBF2 PRX MTMR2 GDAP1 DRP2
6 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.4
7 strabismus 10.1
8 scoliosis 10.1
9 myopia 10.1
10 progressive muscular atrophy 10.1
11 muscular atrophy 10.1
12 mechanical strabismus 10.1
13 infantile scoliosis 10.1
14 charcot-marie-tooth disease, demyelinating, type 1a 9.8 MTMR2 GDAP1
15 axonal neuropathy 9.8 TDP1 GDAP1
16 early-onset glaucoma 9.8 SBF2 MTMR2
17 neuropathy, hereditary, with liability to pressure palsies 9.7 MTMR2 GDAP1
18 charcot-marie-tooth disease, type 4j 9.7 SBF2 MTMR2
19 sensory peripheral neuropathy 9.7 PRX MTMR2 GDAP1
20 charcot-marie-tooth disease and deafness 9.5 MTMR2 GDAP1
21 charcot-marie-tooth disease, type 4b3 9.4 SBF2 MTMR2 GDAP1
22 charcot-marie-tooth disease, axonal, type 2e 9.4 SBF2 MTMR2 GDAP1
23 charcot-marie-tooth disease, type 4b1 9.1 SBF2 PRX MTMR2 GDAP1
24 spinocerebellar ataxia type 1 with axonal neuropathy 8.8 TDP1 SBF2 PRX MTMR2
25 charcot-marie-tooth disease, type 4b2 8.4 TDP1 SBF2 PRX MTMR2 GDAP1
26 charcot-marie-tooth disease, type 4a 8.4 TDP1 SBF2 PRX MTMR2 GDAP1

Graphical network of the top 20 diseases related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:



Diseases related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Human phenotypes related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

32 (show all 14)
# Description HPO Frequency HPO Source Accession
1 vocal cord paresis 32 occasional (7.5%) HP:0001604
2 sensory ataxia 32 occasional (7.5%) HP:0010871
3 scoliosis 32 HP:0002650
4 skeletal muscle atrophy 32 HP:0003202
5 areflexia 32 HP:0001284
6 pes cavus 32 HP:0001761
7 decreased motor nerve conduction velocity 32 HP:0003431
8 motor delay 32 HP:0001270
9 difficulty walking 32 HP:0002355
10 limb muscle weakness 32 HP:0003690
11 peripheral demyelination 32 HP:0011096
12 distal sensory impairment 32 HP:0002936
13 decreased number of large peripheral myelinated nerve fibers 32 HP:0003387
14 basal lamina onion bulb formation 32 HP:0003400

Symptoms via clinical synopsis from OMIM:

57
Skeletal Spine:
scoliosis

Skeletal Feet:
pes cavus

Voice:
vocal cord paresis (reported in 1 patient)

Neurologic Peripheral Nervous System:
areflexia
difficulty walking
distal sensory impairment
decreased motor nerve conduction velocity (ncv) (less than 38 m/s)
loss of large myelinated fibers
more
Neurologic Central Nervous System:
delayed motor development
sensory ataxia (less common)

Clinical features from OMIM:

614895

UMLS symptoms related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:


ataxia, sensory

MGI Mouse Phenotypes related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.35 GDAP1 MTMR2 PRX SBF2 TDP1
2 nervous system MP:0003631 9.1 DRP2 GDAP1 MTMR2 PRX SBF2 TDP1

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Genetic Tests for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Genetic tests related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Demyelinating, Type 4f 29 PRX

Anatomical Context for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

41
Skeletal Muscle

Publications for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Articles related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

(show all 24)
# Title Authors PMID Year
1
Late-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation. 38 8 71
22847150 2012
2
A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease. 38 8 71
11157804 2001
3
Mapping of a new locus for autosomal recessive demyelinating Charcot-Marie-Tooth disease to 19q13.1-13.3 in a large consanguineous Lebanese family: exclusion of MAG as a candidate gene. 38 8 71
10848494 2000
4
Periaxin mutations cause a broad spectrum of demyelinating neuropathies. 8 71
12112076 2002
5
Four novel cases of periaxin-related neuropathy and review of the literature. 38 8
21079185 2010
6
Charcot-Marie-Tooth type 4F disease caused by S399fsx410 mutation in the PRX gene. 38 8
16534116 2006
7
Periaxin mutation causes early-onset but slow-progressive Charcot-Marie-Tooth disease. 8
15197604 2004
8
Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview 71
20301532 1998
9
Linkage analysis and whole exome sequencing reveals AHNAK2 as a novel genetic cause for autosomal recessive CMT in a Malaysian family. 38
31011849 2019
10
Direct Binding of the Flexible C-Terminal Segment of Periaxin to β4 Integrin Suggests a Molecular Basis for CMT4F. 38
31024253 2019
11
A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands. 38
29623298 2018
12
[Establishment of L-periaxin gene knock-out RSC96 cell line]. 38
29034641 2016
13
New mutation in periaxin gene causing Charcot Marie Tooth disease in a Puerto Rican young male. 38
24263033 2013
14
[Charcot-Marie-Tooth disease associated with periaxin mutations (CMT4F): Clinical, electrophysiological and genetic analysis of 24 patients]. 38
24011642 2013
15
Novel mutations in the PRX and the MTMR2 genes are responsible for unusual Charcot-Marie-Tooth disease phenotypes. 38
21741241 2011
16
Genetic study of demyelinating form of autosomal-recessive Charcot-Marie-tooth diseases in a Turkish family. 38
19922348 2009
17
Remodeling of motor nerve terminals in demyelinating axons of periaxin-null mice. 38
18205176 2008
18
[Molecular genetics of inherited neuropathies]. 38
17432174 2006
19
[Molecular genetics of inherited neuropathies]. 38
16541790 2006
20
Neuropathology of Charcot-Marie-Tooth and related disorders. 38
16775365 2006
21
The function of the Periaxin gene during nerve repair in a model of CMT4F. 38
12090399 2002
22
Neuropathology of some hereditary conditions affecting central and peripheral nervous system. 38
12094560 2002
23
A second locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 19q13.3. 38
11112660 2001
24
Charcot-Marie-Tooth Neuropathy Type 4 38
20301641 1998

Variations for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

6 (show all 23)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 PRX NM_181882.2(PRX): c.3703G> T (p.Glu1235Ter) single nucleotide variant Pathogenic rs1385904344 19:40900556-40900556 19:40394649-40394649
2 PRX NM_181882.2(PRX): c.2857C> T (p.Arg953Ter) single nucleotide variant Pathogenic rs104894714 19:40901402-40901402 19:40395495-40395495
3 PRX NM_181882.2(PRX): c.2145T> A (p.Cys715Ter) single nucleotide variant Pathogenic rs104894707 19:40902114-40902114 19:40396207-40396207
4 PRX NM_181882.2(PRX): c.3208C> T (p.Arg1070Ter) single nucleotide variant Pathogenic rs104894708 19:40901051-40901051 19:40395144-40395144
5 PRX NM_181882.2(PRX): c.2787del (p.Lys930fs) deletion Pathogenic rs754521978 19:40901472-40901472 19:40395565-40395565
6 PRX NM_181882.2(PRX): c.979del (p.Asp327fs) deletion Pathogenic 19:40903280-40903280 19:40397373-40397373
7 PRX NM_181882.2(PRX): c.2289del (p.Asp765fs) deletion Likely pathogenic rs797045102 19:40901970-40901970 19:40396063-40396063
8 PRX NM_181882.2(PRX): c.1216G> A (p.Ala406Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs117336941 19:40903043-40903043 19:40397136-40397136
9 PRX NM_181882.2(PRX): c.586C> T (p.Arg196Ter) single nucleotide variant Conflicting interpretations of pathogenicity rs104894706 19:40903673-40903673 19:40397766-40397766
10 PRX NM_181882.2(PRX): c.2098del (p.Ala700fs) deletion Conflicting interpretations of pathogenicity rs281865062 19:40902161-40902161 19:40396254-40396254
11 PRX NM_020956.2(PRX): c.247del (p.Leu83fs) deletion Conflicting interpretations of pathogenicity rs281865061 19:40904661-40904661 19:40398754-40398754
12 PRX NM_181882.2(PRX) deletion Uncertain significance rs1555801137 19:40902699-40902776 19:40396792-40396869
13 PRX NM_020956.2(PRX): c.80C> A (p.Thr27Asn) single nucleotide variant Uncertain significance rs1291881750 19:40909717-40909717 19:40403810-40403810
14 PRX NM_181882.2(PRX): c.4318G> A (p.Val1440Met) single nucleotide variant Uncertain significance 19:40899941-40899941 19:40394034-40394034
15 PRX NM_181882.2(PRX): c.1951G> A (p.Asp651Asn) single nucleotide variant Uncertain significance rs3814290 19:40902308-40902308 19:40396401-40396401
16 PRX NM_181882.2(PRX): c.1546C> T (p.Arg516Trp) single nucleotide variant Uncertain significance rs144305922 19:40902713-40902713 19:40396806-40396806
17 PRX NM_181882.2(PRX): c.3769G> A (p.Gly1257Arg) single nucleotide variant Uncertain significance rs200332462 19:40900490-40900490 19:40394583-40394583
18 PRX NM_020956.2(PRX): c.306C> T (p.Thr102=) single nucleotide variant Benign/Likely benign rs744389 19:40904602-40904602 19:40398695-40398695
19 PRX NM_181882.2(PRX): c.3248C> G (p.Pro1083Arg) single nucleotide variant Benign/Likely benign rs3745202 19:40901011-40901011 19:40395104-40395104
20 PRX NM_181882.2(PRX): c.4059_4061GGA[6] (p.Glu1361del) short repeat Benign rs139624657 19:40900180-40900182 19:40394273-40394275
21 PRX NM_181882.2(PRX): c.1483G> C (p.Glu495Gln) single nucleotide variant Benign rs146789340 19:40902776-40902776 19:40396869-40396869
22 PRX NM_181882.2(PRX): c.2655T> C (p.Pro885=) single nucleotide variant Benign rs268672 19:40901604-40901604 19:40395697-40395697
23 PRX NM_181882.2(PRX): c.2763A> G (p.Ile921Met) single nucleotide variant Benign rs268673 19:40901496-40901496 19:40395589-40395589

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f:

74
# Symbol AA change Variation ID SNP ID
1 PRX p.Asp651Asn VAR_069093 rs3814290

Expression for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f.

Pathways for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

GO Terms for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

Cellular components related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 T-tubule GO:0030315 8.96 PRX AHNAK2
2 vacuolar membrane GO:0005774 8.62 SBF2 MTMR2

Biological processes related to Charcot-Marie-Tooth Disease, Demyelinating, Type 4f according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of RNA splicing GO:0043484 8.96 PRX AHNAK2
2 protein tetramerization GO:0051262 8.32 SBF2

Sources for Charcot-Marie-Tooth Disease, Demyelinating, Type 4f

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
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73 UMLS via Orphanet
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