PCWH
MCID: PRP066
MIFTS: 50

Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease (PCWH)

Categories: Ear diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

MalaCards integrated aliases for Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

Name: Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease 57 40 12 29 6 70
Pcwh Syndrome 57 40 12 36 13 15
Pcwh 57 12 58 72
Neurologic Waardenburg-Shah Syndrome 12 58
Peripheral Demyelinating Neuropathy, Central Dysmyelinating Leukodystrophy, Waardenburg Syndrome and Hirschsprung Disease 72
Peripheral Demyelinating Neuropathy-Central Dysmyelinating Leukodystrophy-Hirschsprung Disease-Waardenburg Syndrome 12
Peripheral Demyelinating Neuropathy-Central Dysmyelinating Leukodystrophy-Waardenburg Syndrome-Hirschsprung Disease 58
Waardenburg-Shah Syndrome, Neurologic Variant 57
Waardenburg-Shah Syndrome Neurologic Variant 72
Syndrome, Pcwh 39
Ws4 Plus 58

Characteristics:

Orphanet epidemiological data:

58
peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-waardenburg syndrome-hirschsprung disease
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
phenotype combines features of hirschsprung disease ({142623)}, charcot-marie-tooth disease type 1 (cmt1b, ), waardenburg-shah syndrome , and central dysmyelinating leukodystrophy
variable penetrance of these features


HPO:

31
peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare gastroenterological diseases
Rare otorhinolaryngological diseases
Rare skin diseases
Developmental anomalies during embryogenesis


Summaries for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

KEGG : 36 PCWH syndrome (Peripheral demyelinating neuropathy, Central dysmyelination, Waardenburg syndrome, and Hirschsprung disease) is a rare inherited disorder caused by SOX10 mutations. SOX10 regulates the development and maintenance of neural crest derivatives including Schwann cells, melanocytes, and enteric ganglion cells, and of oligodendrocytes, which are not derived from the neural crest. Accordingly, SOX10 gene mutations result in a wide spectrum of clinical phenotypes involving these cells. It is suggested that the complex neurological phenotypes in PCWH patients likely result from a combination of haploinsufficiency and additive dominant effect.

MalaCards based summary : Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease, also known as pcwh syndrome, is related to waardenburg syndrome, type 2b and waardenburg syndrome, type 3, and has symptoms including ataxia and paraparesis, spastic. An important gene associated with Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease is SOX10 (SRY-Box Transcription Factor 10), and among its related pathways/superpathways are Neural Crest Differentiation and Melanocyte Development and Pigmentation. Affiliated tissues include bone, olfactory bulb and brain, and related phenotypes are intellectual disability and spasticity

Disease Ontology : 12 A syndrome that is characterized by the association of the features of Waardenburg-Shah syndrome (sensorineural hearing loss, pigmentary abnormalities and Hirschsprung disease; see this term) with neurological features, including: neonatal hypotonia, intellectual deficit (of variable severity), nystagmus, progressive spasticity, ataxia and epilepsy, and has material basis in heterozygous mutation in the SRY-box 10 (SOX10) gene on chromosome 22q13.

OMIM® : 57 PCWH syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. (2004) proposed the acronym PCWH for this disorder. (609136) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease: A complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease.

Related Diseases for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Diseases related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 85)
# Related Disease Score Top Affiliating Genes
1 waardenburg syndrome, type 2b 31.7 SOX10 MITF EDN3
2 waardenburg syndrome, type 3 31.3 SOX10 PAX3 MITF EDNRB EDN3
3 waardenburg syndrome, type 2e 31.0 SOX8 SOX10 POLR2F PAX3 MITF EDNRB
4 waardenburg syndrome, type 2a 30.7 SOX10 POLR2F PAX3 MITF EDNRB DCT
5 waardenburg syndrome type 4 29.9 SOX10 POLR2F MITF EDNRB EDN3
6 neuropathy 29.8 SOX10 POLR2F MPZ GJB1 EGR2
7 peripheral nervous system disease 29.8 SOX10 MPZ GJB1 EGR2
8 hirschsprung disease 1 29.4 SOX9 SOX8 SOX10 POLR2F PAX3 MITF
9 waardenburg's syndrome 29.3 SOX9 SOX8 SOX10 POU3F2 POU3F1 POLR2F
10 waardenburg syndrome, type 4a 29.2 SOX10 POLR2F PAX3 MPZ MITF GJB1
11 pupil disease 10.4 MPZ EGR2
12 gallbladder melanoma 10.4 SOX10 MITF
13 argyll robertson pupil 10.3 MPZ EGR2
14 abnormal pupillary function 10.3 MPZ EGR2
15 malignant choroid melanoma 10.3 SOX10 MITF
16 charcot-marie-tooth disease, dominant intermediate a 10.3 MPZ GJB1
17 charcot-marie-tooth disease, axonal, type 2j 10.3 MPZ EGR2
18 slowed nerve conduction velocity, autosomal dominant 10.3 MPZ GJB1
19 charcot-marie-tooth disease, axonal, type 2w 10.3 MPZ GJB1
20 ocular albinism with congenital sensorineural deafness 10.3 PAX3 MITF
21 malignant spindle cell melanoma 10.3 SOX10 MITF
22 autoimmune peripheral neuropathy 10.3 MPZ GJB1
23 albinism, ocular, with late-onset sensorineural deafness 10.3 PAX3 MITF
24 charcot-marie-tooth disease, axonal, type 2i 10.3 MPZ GJB1
25 neurilemmoma 10.3 SOX10 MPZ MITF
26 crest syndrome 10.2 SOX10 EDNRB
27 cochlear disease 10.2 SOX10 EDNRB EDN3
28 charcot-marie-tooth disease intermediate type 10.2 MPZ GJB1
29 charcot-marie-tooth disease, type 4c 10.2 SOX10 MPZ GJB1
30 charcot-marie-tooth disease, x-linked recessive, 2 10.2 MPZ GJB1 EGR2
31 charcot-marie-tooth disease, demyelinating, type 1d 10.2 MPZ GJB1 EGR2
32 charcot-marie-tooth disease type x 10.2 MPZ GJB1 EGR2
33 charcot-marie-tooth disease, x-linked dominant, 1 10.2 MPZ GJB1 EGR2
34 charcot-marie-tooth disease, type 4a 10.2 MPZ GJB1 EGR2
35 charcot-marie-tooth disease, type 4d 10.2 MPZ GJB1 EGR2
36 charcot-marie-tooth disease, demyelinating, type 1b 10.2 MPZ GJB1 EGR2
37 neuropathy, hereditary, with liability to pressure palsies 10.2 MPZ GJB1 EGR2
38 charcot-marie-tooth disease, demyelinating, type 1c 10.2 MPZ GJB1 EGR2
39 charcot-marie-tooth disease, type 4b2 10.2 MPZ GJB1 EGR2
40 charcot-marie-tooth disease, dominant intermediate c 10.2 MPZ GJB1
41 intestinal pseudo-obstruction 10.2 SOX10 EDNRB EDN3
42 hereditary neuropathies 10.2 MPZ GJB1
43 sensory peripheral neuropathy 10.2 MPZ GJB1 EGR2
44 charcot-marie-tooth disease, demyelinating, type 4f 10.2 MPZ EGR2
45 campomelic dysplasia 10.2 SOX9 SOX8 SOX10
46 brachial plexus neuropathy 10.2 MPZ GJB1
47 brain oligodendroglioma 10.1 SOX10 FAM83H
48 waardenburg syndrome, type 2c 10.1 SOX10 MITF EDNRB EDN3
49 waardenburg syndrome, type 2d 10.1 SOX10 PAX3 MITF EDNRB
50 charcot-marie-tooth disease, demyelinating, type 1a 10.1 SOX10 MPZ GJB1 EGR2

Graphical network of the top 20 diseases related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:



Diseases related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease

Symptoms & Phenotypes for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Human phenotypes related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

58 31 (show top 50) (show all 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 spasticity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001257
3 abnormal pyramidal sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0007256
4 nystagmus 58 31 very rare (1%) Very frequent (99-80%) HP:0000639
5 ataxia 58 31 very rare (1%) Very frequent (99-80%) HP:0001251
6 constipation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002019
7 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
8 sensorineural hearing impairment 58 31 very rare (1%) Very frequent (99-80%) HP:0000407
9 abdominal pain 58 31 hallmark (90%) Very frequent (99-80%) HP:0002027
10 aganglionic megacolon 58 31 hallmark (90%) Very frequent (99-80%) HP:0002251
11 heterochromia iridis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001100
12 hypopigmented skin patches 58 31 hallmark (90%) Very frequent (99-80%) HP:0001053
13 telecanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000506
14 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
15 ileus 58 31 hallmark (90%) Very frequent (99-80%) HP:0002595
16 seizure 31 very rare (1%) HP:0001250
17 hypotonia 31 hallmark (90%) HP:0001252
18 wide nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000431
19 premature graying of hair 58 31 frequent (33%) Frequent (79-30%) HP:0002216
20 hypopigmentation of hair 58 31 frequent (33%) Frequent (79-30%) HP:0005599
21 prominent nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000426
22 underdeveloped nasal alae 58 31 frequent (33%) Frequent (79-30%) HP:0000430
23 hypogonadism 58 31 frequent (33%) Frequent (79-30%) HP:0000135
24 microcolon 58 31 frequent (33%) Frequent (79-30%) HP:0004388
25 decreased lacrimation 58 31 frequent (33%) Frequent (79-30%) HP:0000633
26 abnormal eyebrow morphology 31 frequent (33%) HP:0000534
27 splenomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001744
28 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
29 hypohidrosis 58 31 very rare (1%) Occasional (29-5%) HP:0000966
30 arrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011675
31 arthrogryposis multiplex congenita 58 31 occasional (7.5%) Occasional (29-5%) HP:0002804
32 cryptorchidism 31 very rare (1%) HP:0000028
33 alacrima 31 very rare (1%) HP:0000522
34 seizures 58 Very frequent (99-80%)
35 muscular hypotonia 58 Very frequent (99-80%)
36 neonatal hypotonia 31 HP:0001319
37 spastic tetraplegia 31 HP:0002510
38 decreased nerve conduction velocity 31 HP:0000762
39 anosmia 31 HP:0000458
40 hypoplasia of the semicircular canal 31 HP:0011382
41 areflexia 31 HP:0001284
42 pes cavus 31 HP:0001761
43 hyporeflexia 31 HP:0001265
44 abnormality of the eyebrow 58 Frequent (79-30%)
45 white forelock 31 HP:0002211
46 white eyebrow 31 HP:0002226
47 white eyelashes 31 HP:0002227
48 spastic paraparesis 31 HP:0002313
49 distal muscle weakness 31 HP:0002460
50 demyelinating peripheral neuropathy 31 HP:0007108

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
nystagmus
heterochromia iridis
alacrima
bright blue eyes

Genitourinary External Genitalia Male:
cryptorchidism

Neurologic Peripheral Nervous System:
areflexia
hyporeflexia
demyelinating peripheral neuropathy
distal sensory impairment
distal muscle weakness due to peripheral neuropathy
more
Skeletal Feet:
pes cavus

Head And Neck Ears:
absent brainstem auditory responses
deafness, sensorineural
enlarged vestibule
small cochlea
abnormally shaped cochlea

Head And Neck Mouth:
parotid gland hypoplasia

Neurologic Central Nervous System:
nystagmus
ataxia
neonatal hypotonia
spastic paraparesis
autonomic dysregulation
more
Head And Neck Nose:
anosmia
olfactory bulb agenesis

Skin Nails Hair Skin:
hypopigmented skin patches

Skin Nails Hair Hair:
white forelock
white eyelashes
white eyebrows

Abdomen Gastrointestinal:
decreased myenteric and submucosal ganglia in the bowel
chronic intestinal pseudoobstruction
hirschsprung disease, long-segment
intestinal aganglionosis

Skeletal Skull:
vestibular malformation seen on temporal bone ct (in some patients)
hypoplasia of the semicircular canals

Clinical features from OMIM®:

609136 (Updated 05-Apr-2021)

UMLS symptoms related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:


ataxia; paraparesis, spastic

GenomeRNAi Phenotypes related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 9.81 GJB1
2 Decreased viability GR00055-A-2 9.81 GJB1
3 Decreased viability GR00221-A-3 9.81 MAP3K13
4 Decreased viability GR00240-S-1 9.81 POLR2F SOX10
5 Decreased viability GR00249-S 9.81 EDN3 GJB1 MPZ POLR2F POU3F1 POU3F2
6 Decreased viability GR00381-A-1 9.81 CA10 EDNRB MPZ
7 Decreased viability GR00381-A-3 9.81 MPZ
8 Decreased viability GR00386-A-1 9.81 CA10 EGR2 MPZ POLR2F SOX8
9 Decreased viability GR00402-S-2 9.81 FAM83H GJB1 LGI4 MAP3K13 MITF MPZ

MGI Mouse Phenotypes related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.15 EDN3 EDNRB EGR2 FAM83H GJB1 LGI4
2 integument MP:0010771 10.06 DCT EDN3 EDNRB EGR2 FAM83H MITF
3 mortality/aging MP:0010768 9.97 EDN3 EDNRB EGR2 FAM83H GJB1 LGI4
4 limbs/digits/tail MP:0005371 9.86 EDNRB EGR2 LGI4 MITF PAX3 SOX10
5 nervous system MP:0003631 9.77 DCT EDN3 EDNRB EGR2 GJB1 LGI4
6 pigmentation MP:0001186 9.17 DCT EDN3 EDNRB MITF MYRF PAX3

Drugs & Therapeutics for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Search Clinical Trials , NIH Clinical Center for Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease

Genetic Tests for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Genetic tests related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

# Genetic test Affiliating Genes
1 Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease 29 SOX10

Anatomical Context for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

MalaCards organs/tissues related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

40
Bone, Olfactory Bulb, Brain

Publications for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Articles related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

(show all 14)
# Title Authors PMID Year
1
Genetic and phenotypic heterogeneity in two novel cases of Waardenburg syndrome type IV. 6 57
19764030 2009
2
Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations. 57 6
15004559 2004
3
Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg-Hirschsprung disease: phenotypes linked by SOX10 mutation. 57 6
12447940 2002
4
Peripheral neuropathy with hypomyelination, chronic intestinal pseudo-obstruction and deafness: a developmental "neural crest syndrome" related to a SOX10 mutation. 6 57
11026454 2000
5
Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain. 57 6
10762540 2000
6
Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation. 57 6
10482261 1999
7
An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome. 57 6
1636383 1992
8
Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4. 61 57
17999358 2007
9
Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations. 57
23237859 2013
10
Translation of SOX10 3' untranslated region causes a complex severe neurocristopathy by generation of a deleterious functional domain. 6
17855451 2007
11
SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism. 57
12189494 2002
12
Novel variants in EDNRB gene in Waardenburg syndrome type II and SOX10 gene in PCWH syndrome. 61
33234331 2021
13
SOX10 structure-function analysis in the chicken neural tube reveals important insights into its role in human neurocristopathies. 61
20308050 2010
14
Sumoylation of the SOX10 transcription factor regulates its transcriptional activity. 61
16494873 2006

Variations for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

ClinVar genetic disease variations for Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

6 (show top 50) (show all 56)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6787G>C SNV Pathogenic 7398 rs74315516 GRCh37: 22:38369964-38369964
GRCh38: 22:37973957-37973957
2 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6974G>T SNV Pathogenic 7399 rs74315518 GRCh37: 22:38370151-38370151
GRCh38: 22:37974144-37974144
3 POLR2F , SOX10 NM_006941.3(SOX10):c.1400_*10delAAAGGGGGCCCT (p.*467Cysext*82) Deletion Pathogenic 7400 rs397515368 GRCh37: 22:38369492-38369503
GRCh38: 22:37973485-37973496
4 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6978G>A SNV Pathogenic 7403 rs74315521 GRCh37: 22:38370155-38370155
GRCh38: 22:37974148-37974148
5 POLR2F , SOX10 NM_006941.3(SOX10):c.797del (p.Gly266fs) Deletion Pathogenic 7411 rs397515371 GRCh37: 22:38370106-38370106
GRCh38: 22:37974099-37974099
6 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+6813del Deletion Pathogenic 7412 rs397515372 GRCh37: 22:38369988-38369988
GRCh38: 22:37973981-37973981
7 SOX10 NM_006941.4(SOX10):c.207_208del (p.Cys71fs) Deletion Pathogenic 872923 GRCh37:
GRCh38:
8 POLR2F , SOX10 NM_006941.4(SOX10):c.1155_1174dup (p.Phe392fs) Duplication Pathogenic 915453 GRCh37: 22:38369728-38369729
GRCh38: 22:37973721-37973722
9 POLR2F , SOX10 NM_006941.4(SOX10):c.425G>C (p.Trp142Ser) SNV Pathogenic 915461 GRCh37: 22:38379367-38379367
GRCh38: 22:37983360-37983360
10 POLR2F , SOX10 NM_006941.4(SOX10):c.941C>A (p.Ser314Ter) SNV Pathogenic 976284 GRCh37: 22:38369962-38369962
GRCh38: 22:37973955-37973955
11 POLR2F , SOX10 NM_006941.4(SOX10):c.404G>A (p.Ser135Asn) SNV Likely pathogenic 816906 rs74315515 GRCh37: 22:38379388-38379388
GRCh38: 22:37983381-37983381
12 POLR2F , SOX10 NM_006941.3(SOX10):c.1127C>G (p.Ser376Ter) SNV Likely pathogenic 133302 rs483353058 GRCh37: 22:38369776-38369776
GRCh38: 22:37973769-37973769
13 POLR2F , SOX10 NM_006941.3(SOX10):c.*158A>G SNV Uncertain significance 341615 rs886057494 GRCh37: 22:38369344-38369344
GRCh38: 22:37973337-37973337
14 POLR2F , SOX10 NM_006941.3(SOX10):c.746T>A (p.Leu249Gln) SNV Uncertain significance 341618 rs886057495 GRCh37: 22:38370157-38370157
GRCh38: 22:37974150-37974150
15 POLR2F , SOX10 NM_006941.3(SOX10):c.*643A>G SNV Uncertain significance 341612 rs886057493 GRCh37: 22:38368859-38368859
GRCh38: 22:37972852-37972852
16 POLR2F , SOX10 NM_006941.3(SOX10):c.*1179G>A SNV Uncertain significance 341607 rs749495956 GRCh37: 22:38368323-38368323
GRCh38: 22:37972316-37972316
17 POLR2F , SOX10 NM_006941.3(SOX10):c.906G>A (p.Pro302=) SNV Uncertain significance 341616 rs774324385 GRCh37: 22:38369997-38369997
GRCh38: 22:37973990-37973990
18 POLR2F , SOX10 NM_006941.3(SOX10):c.334A>G (p.Met112Val) SNV Uncertain significance 547778 rs1555939439 GRCh37: 22:38379458-38379458
GRCh38: 22:37983451-37983451
19 POLR2F , SOX10 NM_006941.4(SOX10):c.*568T>A SNV Uncertain significance 899622 GRCh37: 22:38368934-38368934
GRCh38: 22:37972927-37972927
20 POLR2F , SOX10 NM_006941.4(SOX10):c.628G>A (p.Ala210Thr) SNV Uncertain significance 899689 GRCh37: 22:38373943-38373943
GRCh38: 22:37977936-37977936
21 POLR2F , SOX10 NM_006941.4(SOX10):c.-166C>T SNV Uncertain significance 899754 GRCh37: 22:38380427-38380427
GRCh38: 22:37984420-37984420
22 POLR2F , SOX10 NM_006941.4(SOX10):c.*327G>A SNV Uncertain significance 900753 GRCh37: 22:38369175-38369175
GRCh38: 22:37973168-37973168
23 POLR2F , SOX10 NM_006941.3(SOX10):c.585C>T (p.Ala195=) SNV Uncertain significance 341619 rs751780784 GRCh37: 22:38373986-38373986
GRCh38: 22:37977979-37977979
24 POLR2F , SOX10 NM_006941.3(SOX10):c.*712G>T SNV Uncertain significance 341610 rs377420828 GRCh37: 22:38368790-38368790
GRCh38: 22:37972783-37972783
25 POLR2F , SOX10 NM_006941.3(SOX10):c.-63A>G SNV Uncertain significance 341623 rs886057496 GRCh37: 22:38379854-38379854
GRCh38: 22:37983847-37983847
26 POLR2F , SOX10 NM_006941.4(SOX10):c.644G>A (p.Arg215Gln) SNV Uncertain significance 986733 rs779933527 GRCh37: 22:38373927-38373927
GRCh38: 22:37977920-37977920
27 POLR2F , SOX10 NM_006941.4(SOX10):c.1165G>A (p.Gly389Ser) SNV Uncertain significance 1027697 GRCh37: 22:38369738-38369738
GRCh38: 22:37973731-37973731
28 POLR2F , SOX10 NM_006941.4(SOX10):c.181G>A (p.Gly61Ser) SNV Uncertain significance 1027698 GRCh37: 22:38379611-38379611
GRCh38: 22:37983604-37983604
29 POLR2F , SOX10 NM_006941.4(SOX10):c.*830G>C SNV Uncertain significance 903229 GRCh37: 22:38368672-38368672
GRCh38: 22:37972665-37972665
30 POLR2F , SOX10 NM_006941.4(SOX10):c.918C>T (p.His306=) SNV Uncertain significance 733585 rs200226880 GRCh37: 22:38369985-38369985
GRCh38: 22:37973978-37973978
31 POLR2F , SOX10 NM_006941.4(SOX10):c.-9G>A SNV Uncertain significance 903366 GRCh37: 22:38379800-38379800
GRCh38: 22:37983793-37983793
32 POLR2F , SOX10 NM_006941.4(SOX10):c.-29A>G SNV Uncertain significance 903367 GRCh37: 22:38379820-38379820
GRCh38: 22:37983813-37983813
33 POLR2F , SOX10 NM_006941.4(SOX10):c.1111G>T (p.Asp371Tyr) SNV Uncertain significance 902431 GRCh37: 22:38369792-38369792
GRCh38: 22:37973785-37973785
34 POLR2F , SOX10 NM_006941.4(SOX10):c.1111G>A (p.Asp371Asn) SNV Uncertain significance 902432 GRCh37: 22:38369792-38369792
GRCh38: 22:37973785-37973785
35 POLR2F , SOX10 NM_006941.4(SOX10):c.976G>A (p.Val326Met) SNV Uncertain significance 902433 GRCh37: 22:38369927-38369927
GRCh38: 22:37973920-37973920
36 POLR2F , SOX10 NM_006941.4(SOX10):c.1244C>T (p.Ser415Leu) SNV Uncertain significance 900755 GRCh37: 22:38369659-38369659
GRCh38: 22:37973652-37973652
37 POLR2F , SOX10 NM_006941.4(SOX10):c.202T>C (p.Phe68Leu) SNV Uncertain significance 902511 GRCh37: 22:38379590-38379590
GRCh38: 22:37983583-37983583
38 POLR2F , SOX10 NM_006941.4(SOX10):c.135C>T (p.Ser45=) SNV Uncertain significance 902512 GRCh37: 22:38379657-38379657
GRCh38: 22:37983650-37983650
39 POLR2F , SOX10 NM_006941.3(SOX10):c.975C>T (p.Ala325=) SNV Likely benign 514334 rs760496644 GRCh37: 22:38369928-38369928
GRCh38: 22:37973921-37973921
40 POLR2F , SOX10 NM_006941.3(SOX10):c.*932G>A SNV Likely benign 341609 rs8141371 GRCh37: 22:38368570-38368570
GRCh38: 22:37972563-37972563
41 POLR2F , SOX10 NM_001301130.2(POLR2F):c.293+5240_293+5241del Microsatellite Likely benign 341608 rs577740783 GRCh37: 22:38368415-38368416
GRCh38: 22:37972408-37972409
42 POLR2F , SOX10 NM_006941.3(SOX10):c.507G>A (p.Pro169=) SNV Likely benign 341620 rs199703563 GRCh37: 22:38374064-38374064
GRCh38: 22:37978057-37978057
43 POLR2F , SOX10 NM_006941.4(SOX10):c.249C>T (p.Tyr83=) SNV Likely benign 227079 rs73415876 GRCh37: 22:38379543-38379543
GRCh38: 22:37983536-37983536
44 POLR2F , SOX10 NM_006941.4(SOX10):c.122G>T (p.Gly41Val) SNV Likely benign 341622 rs199750760 GRCh37: 22:38379670-38379670
GRCh38: 22:37983663-37983663
45 POLR2F , SOX10 NM_006941.3(SOX10):c.429-12A>G SNV Benign 341621 rs753723642 GRCh37: 22:38374154-38374154
GRCh38: 22:37978147-37978147
46 POLR2F , SOX10 NM_006941.4(SOX10):c.753G>A (p.Ser251=) SNV Benign 341617 rs376907937 GRCh37: 22:38370150-38370150
GRCh38: 22:37974143-37974143
47 POLR2F , SOX10 NM_006941.3(SOX10):c.*475G>A SNV Benign 341614 rs139883 GRCh37: 22:38369027-38369027
GRCh38: 22:37973020-37973020
48 POLR2F , SOX10 NM_006941.4(SOX10):c.428+10C>G SNV Benign 227080 rs201638602 GRCh37: 22:38379354-38379354
GRCh38: 22:37983347-37983347
49 POLR2F , SOX10 NM_006941.3(SOX10):c.*537G>C SNV Benign 341613 rs565069012 GRCh37: 22:38368965-38368965
GRCh38: 22:37972958-37972958
50 POLR2F , SOX10 NM_006941.4(SOX10):c.18C>T (p.Asp6=) SNV Benign 227078 rs149435516 GRCh37: 22:38379774-38379774
GRCh38: 22:37983767-37983767

UniProtKB/Swiss-Prot genetic disease variations for Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease:

72
# Symbol AA change Variation ID SNP ID
1 SOX10 p.Met112Ile VAR_066748
2 SOX10 p.Asn131His VAR_066749
3 SOX10 p.Lys150Asn VAR_066751
4 SOX10 p.Gln174Pro VAR_066754 rs267607081
5 SOX10 p.Pro175Ala VAR_066755
6 SOX10 p.Pro175Leu VAR_066756
7 SOX10 p.Pro175Arg VAR_066757
8 SOX10 p.Gly321Arg VAR_066758

Expression for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Search GEO for disease gene expression data for Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease.

Pathways for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Pathways related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.18 SOX9 SOX10 PAX3 MPZ MITF GJB1
2 10.74 SOX10 PAX3 MITF

GO Terms for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

Cellular components related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transcription factor complex GO:0005667 9.26 SOX9 SOX8 POU3F2 POU3F1
2 chromatin GO:0000785 9.23 SOX9 SOX8 SOX10 POU3F2 POU3F1 PAX3

Biological processes related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease according to GeneCards Suite gene sharing:

(show all 38)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription by RNA polymerase II GO:0006357 10.19 SOX9 SOX8 SOX10 POU3F2 POU3F1 PAX3
2 positive regulation of transcription by RNA polymerase II GO:0045944 10.18 SOX9 SOX8 SOX10 POU3F2 PAX3 MITF
3 regulation of transcription, DNA-templated GO:0006355 10.16 SOX9 SOX8 SOX10 POU3F2 POU3F1 PAX3
4 positive regulation of gene expression GO:0010628 10.05 SOX9 SOX8 SOX10 POU3F1 MITF
5 negative regulation of apoptotic process GO:0043066 10.02 SOX9 SOX8 SOX10 MPZ MITF EDNRB
6 brain development GO:0007420 9.96 POU3F2 POU3F1 EGR2 CA10
7 positive regulation of transcription, DNA-templated GO:0045893 9.92 SOX9 SOX8 SOX10 POU3F1 PAX3 MYRF
8 epidermis development GO:0008544 9.84 POU3F2 POU3F1 DCT
9 cell fate commitment GO:0045165 9.82 SOX9 SOX8 MITF
10 pigmentation GO:0043473 9.76 MITF EDNRB DCT
11 myelination GO:0042552 9.73 POU3F1 MPZ LGI4 EGR2
12 morphogenesis of an epithelium GO:0002009 9.7 SOX9 SOX8 SOX10
13 negative regulation of myoblast differentiation GO:0045662 9.68 SOX9 SOX8
14 positive regulation of neuroblast proliferation GO:0002052 9.67 SOX10 DCT
15 positive regulation of branching involved in ureteric bud morphogenesis GO:0090190 9.67 SOX9 SOX8
16 vasoconstriction GO:0042310 9.67 EDNRB EDN3
17 myelination in peripheral nervous system GO:0022011 9.67 POU3F2 POU3F1 LGI4
18 neural crest cell migration GO:0001755 9.67 SOX8 SOX10 EDNRB EDN3
19 central nervous system myelination GO:0022010 9.65 SOX10 MYRF
20 developmental pigmentation GO:0048066 9.65 EDNRB DCT
21 positive regulation of myelination GO:0031643 9.65 SOX10 MYRF EGR2
22 Sertoli cell development GO:0060009 9.64 SOX9 SOX8
23 lacrimal gland development GO:0032808 9.63 SOX9 SOX10
24 enteric nervous system development GO:0048484 9.63 SOX8 SOX10 EDNRB
25 ureter morphogenesis GO:0072197 9.62 SOX9 SOX8
26 negative regulation of photoreceptor cell differentiation GO:0046533 9.62 SOX9 SOX8
27 positive regulation of kidney development GO:0090184 9.61 SOX9 SOX8
28 metanephric nephron tubule formation GO:0072289 9.61 SOX9 SOX8
29 astrocyte fate commitment GO:0060018 9.6 SOX9 SOX8
30 vein smooth muscle contraction GO:0014826 9.59 EDNRB EDN3
31 renal vesicle induction GO:0072034 9.58 SOX9 SOX8
32 Schwann cell development GO:0014044 9.58 POU3F2 POU3F1 LGI4
33 retinal rod cell differentiation GO:0060221 9.57 SOX9 SOX8
34 positive regulation of gliogenesis GO:0014015 9.56 SOX8 SOX10
35 oligodendrocyte differentiation GO:0048709 9.56 SOX9 SOX8 SOX10 MYRF
36 peripheral nervous system development GO:0007422 9.46 SOX8 SOX10 EGR2 EDNRB
37 morphogenesis of a branching epithelium GO:0061138 9.13 SOX9 SOX8 SOX10
38 melanocyte differentiation GO:0030318 8.92 SOX10 MITF EDNRB EDN3

Molecular functions related to Peripheral Demyelinating Neuropathy, Central Dysmyelination, Waardenburg Syndrome, and Hirschsprung Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 10.07 SOX9 SOX8 SOX10 POU3F2 POU3F1 POLR2F
2 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.92 SOX9 SOX8 SOX10 POU3F2 POU3F1 PAX3
3 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.91 SOX9 SOX8 SOX10 POU3F2 POU3F1 PAX3
4 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.8 SOX9 SOX10 POU3F2 MITF EGR2
5 sequence-specific double-stranded DNA binding GO:1990837 9.7 SOX9 SOX8 SOX10 POU3F2 POU3F1 PAX3
6 sequence-specific DNA binding GO:0043565 9.5 SOX9 SOX8 POU3F2 POU3F1 PAX3 MYRF
7 HMG box domain binding GO:0071837 9.43 PAX3 EGR2
8 DNA-binding transcription factor activity GO:0003700 9.28 SOX9 SOX8 SOX10 POU3F2 POU3F1 PAX3

Sources for Peripheral Demyelinating Neuropathy, Central Dysmyelination,...

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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