MCID: CHR522
MIFTS: 25

Charcot-Marie-Tooth Disease, Dominant Intermediate E

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Nephrological diseases, Metabolic diseases

Aliases & Classifications for Charcot-Marie-Tooth Disease, Dominant Intermediate E

MalaCards integrated aliases for Charcot-Marie-Tooth Disease, Dominant Intermediate E:

Name: Charcot-Marie-Tooth Disease, Dominant Intermediate E 57 53 29 13 6 73
Cmtdie 57 12 53 59 75
Charcot-Marie-Tooth Neuropathy with Focal Segmental Glomerulonephritis 57 12 53 75
Autosomal Dominant Intermediate Charcot-Marie-Tooth Disease Type E 12 53 59
Charcot-Marie-Tooth Disease Dominant Intermediate E 12 15
Charcot-Marie-Tooth Disease-Nephropathy Syndrome 12 59
Charcot-Marie-Tooth Disease, Dominant, Intermediate Type, E 75
Charcot-Marie-Tooth Disease, Dominant Intermediate, Type E 40
Charcot-Marie-Tooth Disease - Nephropathy 53

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant intermediate charcot-marie-tooth disease type e
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide);

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
median onset of proteinuria is 18 years (range 10 to 21)
median onset of neurologic symptoms is 13 years (range 5 to 28)
progressive disorder regarding both neurologic and renal symptoms


HPO:

32
charcot-marie-tooth disease, dominant intermediate e:
Onset and clinical course progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Charcot-Marie-Tooth Disease, Dominant Intermediate E

UniProtKB/Swiss-Prot : 75 Charcot-Marie-Tooth disease, dominant, intermediate type, E: A 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. The dominant intermediate type E is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. Patients additionally manifest focal segmental glomerulonephritis, proteinuria, progression to end- stage renal disease, and a characteristic histologic pattern on renal biopsy.

MalaCards based summary : Charcot-Marie-Tooth Disease, Dominant Intermediate E, also known as cmtdie, is related to focal segmental glomerulosclerosis 5. An important gene associated with Charcot-Marie-Tooth Disease, Dominant Intermediate E is INF2 (Inverted Formin, FH2 And WH2 Domain Containing). Affiliated tissues include kidney, and related phenotypes are proteinuria and pes cavus

Disease Ontology : 12 A Charcot-Marie-Tooth disease intermediate type that has material basis in heterozygous mutation in the INF2 gene on chromosome 14q32.

OMIM : 57 Autosomal dominant intermediate Charcot-Marie-Tooth disease E with focal segmental glomerulonephritis is characterized by the neurologic features of CMT, including distal muscle weakness and atrophy and distal sensory loss, and the features of FSGS, including proteinuria, progression to end-stage renal disease, and a characteristic histologic pattern on renal biopsy (summary by Boyer et al., 2011). Isolated focal segmental glomerulosclerosis-5 (FSGS5; 613237) is also caused by heterozygous mutation in the INF2 gene. For a discussion of genetic heterogeneity of CMTDI, see 606482. (614455)

Related Diseases for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Diseases in the Charcot-Marie-Tooth Disease, Dominant Intermediate D family:

Charcot-Marie-Tooth Disease, Dominant Intermediate E Charcot-Marie-Tooth Disease, Dominant Intermediate F
Charcot-Marie-Tooth Disease, Recessive Intermediate D Charcot-Marie-Tooth Disease, Dominant Intermediate G

Diseases related to Charcot-Marie-Tooth Disease, Dominant Intermediate E via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 focal segmental glomerulosclerosis 5 11.0

Symptoms & Phenotypes for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Symptoms via clinical synopsis from OMIM:

57
Genitourinary Kidneys:
proteinuria
focal segmental glomerulosclerosis
end-stage renal disease (in some)

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
distal sensory impairment
onion bulb formation
distal limb muscle atrophy due to peripheral neuropathy
more
Head And Neck Ears:
deafness, sensorineural (in some patients)

Skeletal Feet:
pes cavus
hammertoes

Skeletal Hands:
claw hands

Muscle Soft Tissue:
amyotrophy, distal, upper and lower limbs


Clinical features from OMIM:

614455

Human phenotypes related to Charcot-Marie-Tooth Disease, Dominant Intermediate E:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 proteinuria 32 HP:0000093
2 pes cavus 32 HP:0001761
3 areflexia 32 HP:0001284
4 split hand 32 HP:0001171
5 hyporeflexia 32 HP:0001265
6 foot dorsiflexor weakness 32 HP:0009027
7 hammertoe 32 HP:0001765
8 distal muscle weakness 32 HP:0002460
9 steppage gait 32 HP:0003376
10 stage 5 chronic kidney disease 32 occasional (7.5%) HP:0003774
11 distal sensory impairment 32 HP:0002936
12 axonal loss 32 HP:0003447
13 distal lower limb amyotrophy 32 HP:0008944
14 focal segmental glomerulosclerosis 32 HP:0000097
15 onion bulb formation 32 HP:0003383
16 distal upper limb amyotrophy 32 HP:0007149

GenomeRNAi Phenotypes related to Charcot-Marie-Tooth Disease, Dominant Intermediate E according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased focal adhesion (FA) area, decreased FA length, decreased FA mean intensity, increased number of small and round FAs, increased FA abundance GR00210-A 8.62 ACTB INF2

Drugs & Therapeutics for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Search Clinical Trials , NIH Clinical Center for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Genetic Tests for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Genetic tests related to Charcot-Marie-Tooth Disease, Dominant Intermediate E:

# Genetic test Affiliating Genes
1 Charcot-Marie-Tooth Disease, Dominant Intermediate E 29 INF2

Anatomical Context for Charcot-Marie-Tooth Disease, Dominant Intermediate E

MalaCards organs/tissues related to Charcot-Marie-Tooth Disease, Dominant Intermediate E:

41
Kidney

Publications for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Variations for Charcot-Marie-Tooth Disease, Dominant Intermediate E

UniProtKB/Swiss-Prot genetic disease variations for Charcot-Marie-Tooth Disease, Dominant Intermediate E:

75
# Symbol AA change Variation ID SNP ID
1 INF2 p.Glu184Lys VAR_063077
2 INF2 p.Cys104Phe VAR_067589 rs387907035
3 INF2 p.Cys104Arg VAR_067590 rs387907034
4 INF2 p.Cys104Trp VAR_067591 rs387907036
5 INF2 p.Leu128Pro VAR_067592 rs387907037
6 INF2 p.Leu132Arg VAR_067593 rs387907038
7 INF2 p.Val105Gly VAR_073988
8 INF2 p.Leu132Pro VAR_073990

ClinVar genetic disease variations for Charcot-Marie-Tooth Disease, Dominant Intermediate E:

6
(show top 50) (show all 244)
# Gene Variation Type Significance SNP ID Assembly Location
1 INF2 NM_022489.3(INF2): c.310T> C (p.Cys104Arg) single nucleotide variant Pathogenic rs387907034 GRCh37 Chromosome 14, 105168012: 105168012
2 INF2 NM_022489.3(INF2): c.310T> C (p.Cys104Arg) single nucleotide variant Pathogenic rs387907034 GRCh38 Chromosome 14, 104701675: 104701675
3 INF2 NM_022489.3(INF2): c.311G> T (p.Cys104Phe) single nucleotide variant Pathogenic rs387907035 GRCh37 Chromosome 14, 105168013: 105168013
4 INF2 NM_022489.3(INF2): c.311G> T (p.Cys104Phe) single nucleotide variant Pathogenic rs387907035 GRCh38 Chromosome 14, 104701676: 104701676
5 INF2 NM_022489.3(INF2): c.312C> G (p.Cys104Trp) single nucleotide variant Pathogenic rs387907036 GRCh37 Chromosome 14, 105168014: 105168014
6 INF2 NM_022489.3(INF2): c.312C> G (p.Cys104Trp) single nucleotide variant Pathogenic rs387907036 GRCh38 Chromosome 14, 104701677: 104701677
7 INF2 NM_022489.3(INF2): c.383T> C (p.Leu128Pro) single nucleotide variant Likely pathogenic rs387907037 GRCh37 Chromosome 14, 105168085: 105168085
8 INF2 NM_022489.3(INF2): c.383T> C (p.Leu128Pro) single nucleotide variant Likely pathogenic rs387907037 GRCh38 Chromosome 14, 104701748: 104701748
9 INF2 NM_022489.3(INF2): c.395T> G (p.Leu132Arg) single nucleotide variant Pathogenic rs387907038 GRCh37 Chromosome 14, 105169445: 105169445
10 INF2 NM_022489.3(INF2): c.395T> G (p.Leu132Arg) single nucleotide variant Pathogenic rs387907038 GRCh38 Chromosome 14, 104703108: 104703108
11 INF2 INF2, 9-BP DEL, NT490 deletion Pathogenic
12 INF2 NM_022489.3(INF2): c.67T> A (p.Ser23Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs746964937 GRCh38 Chromosome 14, 104701432: 104701432
13 INF2 NM_022489.3(INF2): c.67T> A (p.Ser23Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs746964937 GRCh37 Chromosome 14, 105167769: 105167769
14 INF2 NM_022489.3(INF2): c.3221G> A (p.Arg1074Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs201445955 GRCh38 Chromosome 14, 104714383: 104714383
15 INF2 NM_022489.3(INF2): c.3221G> A (p.Arg1074Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs201445955 GRCh37 Chromosome 14, 105180720: 105180720
16 INF2 NM_022489.3(INF2): c.42G> A (p.Leu14=) single nucleotide variant Benign rs62638758 GRCh38 Chromosome 14, 104701407: 104701407
17 INF2 NM_022489.3(INF2): c.42G> A (p.Leu14=) single nucleotide variant Benign rs62638758 GRCh37 Chromosome 14, 105167744: 105167744
18 INF2 NM_022489.3(INF2): c.391+6C> T single nucleotide variant Benign rs75115369 GRCh38 Chromosome 14, 104701762: 104701762
19 INF2 NM_022489.3(INF2): c.391+6C> T single nucleotide variant Benign rs75115369 GRCh37 Chromosome 14, 105168099: 105168099
20 INF2 NM_022489.3(INF2): c.879G> A (p.Ser293=) single nucleotide variant Benign/Likely benign rs184709736 GRCh37 Chromosome 14, 105173282: 105173282
21 INF2 NM_022489.3(INF2): c.879G> A (p.Ser293=) single nucleotide variant Benign/Likely benign rs184709736 GRCh38 Chromosome 14, 104706945: 104706945
22 INF2 NM_022489.3(INF2): c.2322C> T (p.Thr774=) single nucleotide variant Benign rs59751492 GRCh37 Chromosome 14, 105177427: 105177427
23 INF2 NM_022489.3(INF2): c.2322C> T (p.Thr774=) single nucleotide variant Benign rs59751492 GRCh38 Chromosome 14, 104711090: 104711090
24 INF2 NM_022489.3(INF2): c.2458C> T (p.Arg820Trp) single nucleotide variant Benign/Likely benign rs79327775 GRCh38 Chromosome 14, 104711668: 104711668
25 INF2 NM_022489.3(INF2): c.2458C> T (p.Arg820Trp) single nucleotide variant Benign/Likely benign rs79327775 GRCh37 Chromosome 14, 105178005: 105178005
26 INF2 NM_022489.3(INF2): c.2571C> T (p.Ser857=) single nucleotide variant Benign rs62640005 GRCh38 Chromosome 14, 104712514: 104712514
27 INF2 NM_022489.3(INF2): c.2571C> T (p.Ser857=) single nucleotide variant Benign rs62640005 GRCh37 Chromosome 14, 105178851: 105178851
28 INF2 NM_022489.3(INF2): c.2630G> A (p.Arg877Gln) single nucleotide variant Benign/Likely benign rs142678449 GRCh38 Chromosome 14, 104712847: 104712847
29 INF2 NM_022489.3(INF2): c.2630G> A (p.Arg877Gln) single nucleotide variant Benign/Likely benign rs142678449 GRCh37 Chromosome 14, 105179184: 105179184
30 INF2 NM_022489.3(INF2): c.3069C> T (p.Pro1023=) single nucleotide variant Benign/Likely benign rs75382114 GRCh37 Chromosome 14, 105180568: 105180568
31 INF2 NM_022489.3(INF2): c.3069C> T (p.Pro1023=) single nucleotide variant Benign/Likely benign rs75382114 GRCh38 Chromosome 14, 104714231: 104714231
32 INF2 NM_022489.3(INF2): c.3108T> C (p.Leu1036=) single nucleotide variant Benign/Likely benign rs186075307 GRCh37 Chromosome 14, 105180607: 105180607
33 INF2 NM_022489.3(INF2): c.3108T> C (p.Leu1036=) single nucleotide variant Benign/Likely benign rs186075307 GRCh38 Chromosome 14, 104714270: 104714270
34 INF2 NM_022489.3(INF2): c.3153C> T (p.Asp1051=) single nucleotide variant Benign rs117457867 GRCh37 Chromosome 14, 105180652: 105180652
35 INF2 NM_022489.3(INF2): c.3153C> T (p.Asp1051=) single nucleotide variant Benign rs117457867 GRCh38 Chromosome 14, 104714315: 104714315
36 INF2 NM_022489.3(INF2): c.3404C> T (p.Thr1135Met) single nucleotide variant Benign/Likely benign rs3803311 GRCh37 Chromosome 14, 105180903: 105180903
37 INF2 NM_022489.3(INF2): c.3404C> T (p.Thr1135Met) single nucleotide variant Benign/Likely benign rs3803311 GRCh38 Chromosome 14, 104714566: 104714566
38 INF2 NM_022489.3(INF2): c.3747G> A (p.Gln1249=) single nucleotide variant Benign rs149939482 GRCh37 Chromosome 14, 105181673: 105181673
39 INF2 NM_022489.3(INF2): c.3747G> A (p.Gln1249=) single nucleotide variant Benign rs149939482 GRCh38 Chromosome 14, 104715336: 104715336
40 INF2 NM_022489.3(INF2): c.1770C> T (p.Pro590=) single nucleotide variant Conflicting interpretations of pathogenicity rs549506051 GRCh38 Chromosome 14, 104708470: 104708470
41 INF2 NM_022489.3(INF2): c.1770C> T (p.Pro590=) single nucleotide variant Conflicting interpretations of pathogenicity rs549506051 GRCh37 Chromosome 14, 105174807: 105174807
42 INF2 NM_022489.3(INF2): c.2053A> G (p.Ile685Val) single nucleotide variant Conflicting interpretations of pathogenicity rs199526439 GRCh38 Chromosome 14, 104709620: 104709620
43 INF2 NM_022489.3(INF2): c.2053A> G (p.Ile685Val) single nucleotide variant Conflicting interpretations of pathogenicity rs199526439 GRCh37 Chromosome 14, 105175957: 105175957
44 INF2 NM_022489.3(INF2): c.3134G> A (p.Arg1045Gln) single nucleotide variant Benign/Likely benign rs200369827 GRCh38 Chromosome 14, 104714296: 104714296
45 INF2 NM_022489.3(INF2): c.3134G> A (p.Arg1045Gln) single nucleotide variant Benign/Likely benign rs200369827 GRCh37 Chromosome 14, 105180633: 105180633
46 INF2 NM_022489.3(INF2): c.3206C> T (p.Pro1069Leu) single nucleotide variant Uncertain significance rs376139171 GRCh38 Chromosome 14, 104714368: 104714368
47 INF2 NM_022489.3(INF2): c.3206C> T (p.Pro1069Leu) single nucleotide variant Uncertain significance rs376139171 GRCh37 Chromosome 14, 105180705: 105180705
48 INF2 NM_022489.3(INF2): c.507+7G> A single nucleotide variant Benign/Likely benign rs201568246 GRCh37 Chromosome 14, 105169564: 105169564
49 INF2 NM_022489.3(INF2): c.507+7G> A single nucleotide variant Benign/Likely benign rs201568246 GRCh38 Chromosome 14, 104703227: 104703227
50 INF2 NM_022489.3(INF2): c.1755G> A (p.Ala585=) single nucleotide variant Benign/Likely benign rs375573206 GRCh38 Chromosome 14, 104708455: 104708455

Expression for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Search GEO for disease gene expression data for Charcot-Marie-Tooth Disease, Dominant Intermediate E.

Pathways for Charcot-Marie-Tooth Disease, Dominant Intermediate E

GO Terms for Charcot-Marie-Tooth Disease, Dominant Intermediate E

Sources for Charcot-Marie-Tooth Disease, Dominant Intermediate E

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
Content
Loading form....