CMT4F
MCID: CHR670
MIFTS: 34

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 58 30 6 74
Charcot-Marie-Tooth Disease Type 4f 12 54 60 15
Cmt4f 58 12 60 76
Charcot-Marie-Tooth Disease, Type 4f 58 13 41
Charcot-Marie-Tooth Disease Demyelinating Autosomal Recessive 4f 76
Charcot-Marie-Tooth Neuropathy Type 4f 76
Charcot-Marie-Tooth Disease 4f 76
Dejerine-Sottas Disease 74

Characteristics:

Orphanet epidemiological data:

60
charcot-marie-tooth disease type 4f
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal recessive

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


HPO:

33
charcot-marie-tooth disease, demyelinating, type 4f:
Onset and clinical course slow progression
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


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

UniProtKB/Swiss-Prot : 76 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 tooth 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 : 58 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 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 4f via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
# Related Disease Score Top Affiliating Genes
1 hypertrophic neuropathy of dejerine-sottas 32.0 DRP2 GDAP1 MTMR2 PRX
2 tooth disease 29.3 GDAP1 MTMR2 PRX SBF2
3 charcot-marie-tooth disease 28.9 DRP2 GDAP1 MTMR2 PRX SBF2
4 neuropathy, congenital hypomyelinating, 1, autosomal recessive 11.3
5 charcot-marie-tooth disease, demyelinating, type 1a 9.8 GDAP1 MTMR2
6 neuropathy, hereditary, with liability to pressure palsies 9.7 GDAP1 MTMR2
7 early-onset glaucoma 9.7 MTMR2 SBF2
8 sensory peripheral neuropathy 9.7 GDAP1 MTMR2 PRX
9 peripheral nervous system disease 9.7 GDAP1 MTMR2 PRX
10 charcot-marie-tooth disease, type 4j 9.7 MTMR2 SBF2
11 charcot-marie-tooth disease and deafness 9.6 GDAP1 MTMR2
12 neuropathy 9.6 GDAP1 PRX SBF2
13 spinocerebellar ataxia type 1 with axonal neuropathy 9.5 MTMR2 PRX SBF2
14 charcot-marie-tooth disease, type 4b3 9.5 GDAP1 MTMR2 SBF2
15 charcot-marie-tooth disease, axonal, type 2e 9.4 GDAP1 MTMR2 SBF2
16 charcot-marie-tooth disease, type 4b2 9.2 GDAP1 MTMR2 PRX SBF2
17 charcot-marie-tooth disease, type 4a 9.2 GDAP1 MTMR2 PRX SBF2
18 charcot-marie-tooth disease, type 4b1 9.2 GDAP1 MTMR2 PRX SBF2

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:

33 (show all 14)
# Description HPO Frequency HPO Source Accession
1 vocal cord paresis 33 occasional (7.5%) HP:0001604
2 sensory ataxia 33 occasional (7.5%) HP:0010871
3 scoliosis 33 HP:0002650
4 skeletal muscle atrophy 33 HP:0003202
5 pes cavus 33 HP:0001761
6 decreased motor nerve conduction velocity 33 HP:0003431
7 motor delay 33 HP:0001270
8 areflexia 33 HP:0001284
9 difficulty walking 33 HP:0002355
10 limb muscle weakness 33 HP:0003690
11 peripheral demyelination 33 HP:0011096
12 distal sensory impairment 33 HP:0002936
13 decreased number of large peripheral myelinated nerve fibers 33 HP:0003387
14 basal lamina onion bulb formation 33 HP:0003400

Symptoms via clinical synopsis from OMIM:

58
Skeletal Spine:
scoliosis

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
Voice:
vocal cord paresis (reported in 1 patient)

Skeletal Feet:
pes cavus

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:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.02 DRP2 GDAP1 MTMR2 PRX SBF2

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 30 PRX

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

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

42
Skeletal Muscle

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

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

# Title Authors Year
1
Direct Binding of the Flexible C-Terminal Segment of Periaxin to β4 Integrin Suggests a Molecular Basis for CMT4F. ( 31024253 )
2019
2
Late-onset Charcot-Marie-Tooth disease 4F caused by periaxin gene mutation. ( 22847150 )
2012
3
[A pedigree of Charcot-Marie-Tooth disease type 4F (Periaxin mutation)]. ( 15835292 )
2005
4
The function of the Periaxin gene during nerve repair in a model of CMT4F. ( 12090399 )
2002
5
Periaxin mutations cause a broad spectrum of demyelinating neuropathies. ( 12112076 )
2002
6
A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease. ( 11157804 )
2001
7
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. ( 10848494 )
2000

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

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

76
# Symbol AA change Variation ID SNP ID
1 PRX p.Asp651Asn VAR_069093 rs3814290

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

6 (show all 40)
# Gene Variation Type Significance SNP ID Assembly Location
1 PRX NM_181882.2(PRX): c.2857C> T (p.Arg953Ter) single nucleotide variant Pathogenic rs104894714 GRCh37 Chromosome 19, 40901402: 40901402
2 PRX NM_181882.2(PRX): c.2857C> T (p.Arg953Ter) single nucleotide variant Pathogenic rs104894714 GRCh38 Chromosome 19, 40395495: 40395495
3 PRX NM_181882.2(PRX): c.586C> T (p.Arg196Ter) single nucleotide variant Pathogenic rs104894706 GRCh37 Chromosome 19, 40903673: 40903673
4 PRX NM_181882.2(PRX): c.586C> T (p.Arg196Ter) single nucleotide variant Pathogenic rs104894706 GRCh38 Chromosome 19, 40397766: 40397766
5 PRX NM_181882.2(PRX): c.2145T> A (p.Cys715Ter) single nucleotide variant Pathogenic rs104894707 GRCh37 Chromosome 19, 40902114: 40902114
6 PRX NM_181882.2(PRX): c.2145T> A (p.Cys715Ter) single nucleotide variant Pathogenic rs104894707 GRCh38 Chromosome 19, 40396207: 40396207
7 PRX NM_181882.2(PRX): c.3208C> T (p.Arg1070Ter) single nucleotide variant Pathogenic rs104894708 GRCh37 Chromosome 19, 40901051: 40901051
8 PRX NM_181882.2(PRX): c.3208C> T (p.Arg1070Ter) single nucleotide variant Pathogenic rs104894708 GRCh38 Chromosome 19, 40395144: 40395144
9 PRX NM_181882.2(PRX): c.1951G> A (p.Asp651Asn) single nucleotide variant Uncertain significance rs3814290 GRCh37 Chromosome 19, 40902308: 40902308
10 PRX NM_181882.2(PRX): c.1951G> A (p.Asp651Asn) single nucleotide variant Uncertain significance rs3814290 GRCh38 Chromosome 19, 40396401: 40396401
11 PRX NM_181882.2(PRX): c.2098delG (p.Ala700Profs) deletion Pathogenic rs281865062 GRCh37 Chromosome 19, 40902161: 40902161
12 PRX NM_181882.2(PRX): c.2098delG (p.Ala700Profs) deletion Pathogenic rs281865062 GRCh38 Chromosome 19, 40396254: 40396254
13 PRX NM_181882.2(PRX): c.247delC (p.Leu83Cysfs) deletion Pathogenic rs281865061 GRCh37 Chromosome 19, 40904661: 40904661
14 PRX NM_181882.2(PRX): c.247delC (p.Leu83Cysfs) deletion Pathogenic rs281865061 GRCh38 Chromosome 19, 40398754: 40398754
15 PRX NM_181882.2(PRX): c.2655T> C (p.Pro885=) single nucleotide variant Benign rs268672 GRCh37 Chromosome 19, 40901604: 40901604
16 PRX NM_181882.2(PRX): c.2655T> C (p.Pro885=) single nucleotide variant Benign rs268672 GRCh38 Chromosome 19, 40395697: 40395697
17 PRX NM_181882.2(PRX): c.2763A> G (p.Ile921Met) single nucleotide variant Benign rs268673 GRCh37 Chromosome 19, 40901496: 40901496
18 PRX NM_181882.2(PRX): c.2763A> G (p.Ile921Met) single nucleotide variant Benign rs268673 GRCh38 Chromosome 19, 40395589: 40395589
19 PRX NM_181882.2(PRX): c.306C> T (p.Thr102=) single nucleotide variant Benign/Likely benign rs744389 GRCh37 Chromosome 19, 40904602: 40904602
20 PRX NM_181882.2(PRX): c.306C> T (p.Thr102=) single nucleotide variant Benign/Likely benign rs744389 GRCh38 Chromosome 19, 40398695: 40398695
21 PRX NM_181882.2(PRX): c.3248C> G (p.Pro1083Arg) single nucleotide variant Benign/Likely benign rs3745202 GRCh37 Chromosome 19, 40901011: 40901011
22 PRX NM_181882.2(PRX): c.3248C> G (p.Pro1083Arg) single nucleotide variant Benign/Likely benign rs3745202 GRCh38 Chromosome 19, 40395104: 40395104
23 PRX NM_181882.2(PRX): c.2289delT (p.Asp765Thrfs) deletion Likely pathogenic rs797045102 GRCh37 Chromosome 19, 40901970: 40901970
24 PRX NM_181882.2(PRX): c.2289delT (p.Asp765Thrfs) deletion Likely pathogenic rs797045102 GRCh38 Chromosome 19, 40396063: 40396063
25 PRX NM_181882.2(PRX): c.4077_4079delGGA (p.Glu1361del) deletion Benign rs139624657 GRCh37 Chromosome 19, 40900180: 40900182
26 PRX NM_181882.2(PRX): c.4077_4079delGGA (p.Glu1361del) deletion Benign rs139624657 GRCh38 Chromosome 19, 40394273: 40394275
27 PRX NM_181882.2(PRX): c.1483G> C (p.Glu495Gln) single nucleotide variant Benign rs146789340 GRCh38 Chromosome 19, 40396869: 40396869
28 PRX NM_181882.2(PRX): c.1483G> C (p.Glu495Gln) single nucleotide variant Benign rs146789340 GRCh37 Chromosome 19, 40902776: 40902776
29 PRX NM_181882.2(PRX): c.2787del (p.Lys930Serfs) deletion Pathogenic rs754521978 GRCh38 Chromosome 19, 40395565: 40395565
30 PRX NM_181882.2(PRX): c.2787del (p.Lys930Serfs) deletion Pathogenic rs754521978 GRCh37 Chromosome 19, 40901472: 40901472
31 PRX NM_181882.2(PRX): c.1216G> A (p.Ala406Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs117336941 GRCh37 Chromosome 19, 40903043: 40903043
32 PRX NM_181882.2(PRX): c.1216G> A (p.Ala406Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs117336941 GRCh38 Chromosome 19, 40397136: 40397136
33 PRX NM_181882.2(PRX): c.3769G> A (p.Gly1257Arg) single nucleotide variant Uncertain significance rs200332462 GRCh37 Chromosome 19, 40900490: 40900490
34 PRX NM_181882.2(PRX): c.3769G> A (p.Gly1257Arg) single nucleotide variant Uncertain significance rs200332462 GRCh38 Chromosome 19, 40394583: 40394583
35 PRX NM_181882.2(PRX): c.1546C> T (p.Arg516Trp) single nucleotide variant Uncertain significance rs144305922 GRCh38 Chromosome 19, 40396806: 40396806
36 PRX NM_181882.2(PRX): c.1546C> T (p.Arg516Trp) single nucleotide variant Uncertain significance rs144305922 GRCh37 Chromosome 19, 40902713: 40902713
37 PRX NM_020956.2(PRX): c.80C> A (p.Thr27Asn) single nucleotide variant Uncertain significance rs1291881750 GRCh37 Chromosome 19, 40909717: 40909717
38 PRX NM_020956.2(PRX): c.80C> A (p.Thr27Asn) single nucleotide variant Uncertain significance rs1291881750 GRCh38 Chromosome 19, 40403810: 40403810
39 PRX NM_181882.2(PRX): c.3703G> T (p.Glu1235Ter) single nucleotide variant Pathogenic rs1385904344 GRCh38 Chromosome 19, 40394649: 40394649
40 PRX NM_181882.2(PRX): c.3703G> T (p.Glu1235Ter) single nucleotide variant Pathogenic rs1385904344 GRCh37 Chromosome 19, 40900556: 40900556

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 AHNAK2 PRX
2 vacuolar membrane GO:0005774 8.62 MTMR2 SBF2

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 AHNAK2 PRX
2 protein tetramerization GO:0051262 8.32 SBF2

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

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