MCID: WRD032
MIFTS: 39

Waardenburg Syndrome, Type 2a

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

Aliases & Classifications for Waardenburg Syndrome, Type 2a

MalaCards integrated aliases for Waardenburg Syndrome, Type 2a:

Name: Waardenburg Syndrome, Type 2a 57 13 40
Waardenburg Syndrome Type 2a 12 76 53 29 6
Ws2a 57 12 53 75
Waardenburg Syndrome, Type Iia 57 73
Waardenburg Syndrome Without Dystopia Canthorum 57
Waardenburg Syndrome Type Iia 12
Waardenburg Syndrome 2a 75
Ws2 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable expressivity of each feature
genetic heterogeneity of waardenburg syndrome type 2
other variants of waardenburg syndrome include waardenburg syndrome type 1 , waardenburg syndrome type 3 , and waardenburg syndrome type 4


HPO:

32
waardenburg syndrome, type 2a:
Onset and clinical course variable expressivity
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Waardenburg Syndrome, Type 2a

OMIM : 57 Waardenburg syndrome type 2 is an autosomal dominant auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi, which is seen in some other forms of WS (reviews by Read and Newton, 1997 and Pingault et al., 2010). (193510)

MalaCards based summary : Waardenburg Syndrome, Type 2a, also known as waardenburg syndrome type 2a, is related to waardenburg syndrome, type 2e and waardenburg's syndrome. An important gene associated with Waardenburg Syndrome, Type 2a is MITF (Melanogenesis Associated Transcription Factor), and among its related pathways/superpathways are Transcriptional misregulation in cancer and Mitophagy - animal. Affiliated tissues include skin and eye, and related phenotypes are underdeveloped nasal alae and wide nasal bridge

UniProtKB/Swiss-Prot : 75 Waardenburg syndrome 2A: WS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1.

Disease Ontology : 12 A Waardenburg's syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and absence of lateral displacement of the inner canthus of each eye that has material basis in heterozygous mutation in the MITF gene on chromosome 3p13.

Wikipedia : 76 Waardenburg syndrome is a rare genetic disorder most often characterized by varying degrees of deafness,... more...

Related Diseases for Waardenburg Syndrome, Type 2a

Graphical network of the top 20 diseases related to Waardenburg Syndrome, Type 2a:



Diseases related to Waardenburg Syndrome, Type 2a

Symptoms & Phenotypes for Waardenburg Syndrome, Type 2a

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Nose:
wide nasal bridge
hypoplastic alae nasi

Skin Nails Hair Hair:
premature graying of hair
white forelock
white eyelashes and eyebrows

Head And Neck Ears:
deafness, congenital sensorineural

Head And Neck Eyes:
heterochromia iridis
synophrys
hypoplastic iris stoma
dystopia canthorum absent

Skin Nails Hair Skin:
congenital partial albinism (leukoderma) on face, trunk, or limbs


Clinical features from OMIM:

193510

Human phenotypes related to Waardenburg Syndrome, Type 2a:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 underdeveloped nasal alae 32 HP:0000430
2 wide nasal bridge 32 HP:0000431
3 synophrys 32 HP:0000664
4 albinism 32 HP:0001022
5 heterochromia iridis 32 HP:0001100
6 white forelock 32 HP:0002211
7 premature graying of hair 32 HP:0002216
8 white eyebrow 32 HP:0002226
9 white eyelashes 32 HP:0002227
10 partial albinism 32 HP:0007443
11 hypoplastic iris stroma 32 HP:0007990
12 congenital sensorineural hearing impairment 32 HP:0008527

GenomeRNAi Phenotypes related to Waardenburg Syndrome, Type 2a according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased ionizing radiation sensitivity GR00232-A-1 8.8 EDNRB MITF TFE3

MGI Mouse Phenotypes related to Waardenburg Syndrome, Type 2a:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.5 EDNRB MITF TFE3
2 integument MP:0010771 9.43 EDNRB MITF TFE3
3 pigmentation MP:0001186 9.33 EDNRB MITF TFE3
4 skeleton MP:0005390 9.13 EDNRB MITF TFE3
5 vision/eye MP:0005391 8.8 EDNRB MITF TFE3

Drugs & Therapeutics for Waardenburg Syndrome, Type 2a

Search Clinical Trials , NIH Clinical Center for Waardenburg Syndrome, Type 2a

Genetic Tests for Waardenburg Syndrome, Type 2a

Genetic tests related to Waardenburg Syndrome, Type 2a:

# Genetic test Affiliating Genes
1 Waardenburg Syndrome Type 2a 29 MITF

Anatomical Context for Waardenburg Syndrome, Type 2a

MalaCards organs/tissues related to Waardenburg Syndrome, Type 2a:

41
Skin, Eye

Publications for Waardenburg Syndrome, Type 2a

Articles related to Waardenburg Syndrome, Type 2a:

# Title Authors Year
1
Creation of miniature pig model of human Waardenburg syndrome type 2A by ENU mutagenesis. ( 29094203 )
2017
2
Evidence to suggest that expression of MITF induces melanocyte differentiation and haploinsufficiency of MITF causes Waardenburg syndrome type 2A. ( 9170159 )
1997
3
Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A. ( 8659547 )
1996

Variations for Waardenburg Syndrome, Type 2a

UniProtKB/Swiss-Prot genetic disease variations for Waardenburg Syndrome, Type 2a:

75
# Symbol AA change Variation ID SNP ID
1 MITF p.Ser357Pro VAR_010300 rs104893744
2 MITF p.Asn385Asp VAR_010301
3 MITF p.Ser405Pro VAR_010302 rs104893747

ClinVar genetic disease variations for Waardenburg Syndrome, Type 2a:

6
(show all 38)
# Gene Variation Type Significance SNP ID Assembly Location
1 MITF NM_000248.3(MITF): c.33+1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 3, 69985907: 69985907
2 MITF NM_000248.3(MITF): c.33+1G> A single nucleotide variant Pathogenic GRCh38 Chromosome 3, 69936756: 69936756
3 MITF NM_000248.3(MITF): c.442-2A> C single nucleotide variant Pathogenic GRCh38 Chromosome 3, 69949049: 69949049
4 MITF NM_000248.3(MITF): c.442-2A> C single nucleotide variant Pathogenic GRCh37 Chromosome 3, 69998200: 69998200
5 MITF NM_198159.2(MITF): c.1051T> C (p.Ser351Pro) single nucleotide variant Pathogenic rs104893744 GRCh37 Chromosome 3, 70008461: 70008461
6 MITF NM_198159.2(MITF): c.1051T> C (p.Ser351Pro) single nucleotide variant Pathogenic rs104893744 GRCh38 Chromosome 3, 69959310: 69959310
7 MITF NM_000248.3(MITF): c.824delA (p.Glu275Glyfs) deletion Pathogenic GRCh37 Chromosome 3, 70008537: 70008537
8 MITF NM_000248.3(MITF): c.824delA (p.Glu275Glyfs) deletion Pathogenic GRCh38 Chromosome 3, 69959386: 69959386
9 MITF NM_198159.2(MITF): c.943C> T (p.Arg315Ter) single nucleotide variant Pathogenic rs104893746 GRCh37 Chromosome 3, 70005611: 70005611
10 MITF NM_198159.2(MITF): c.943C> T (p.Arg315Ter) single nucleotide variant Pathogenic rs104893746 GRCh38 Chromosome 3, 69956460: 69956460
11 MITF NM_198159.2(MITF): c.1195T> C (p.Ser399Pro) single nucleotide variant Pathogenic rs104893747 GRCh37 Chromosome 3, 70014031: 70014031
12 MITF NM_198159.2(MITF): c.1195T> C (p.Ser399Pro) single nucleotide variant Pathogenic rs104893747 GRCh38 Chromosome 3, 69964880: 69964880
13 EDNRB NM_000115.4(EDNRB): c.914G> A (p.Ser305Asn) single nucleotide variant risk factor rs5352 GRCh37 Chromosome 13, 78475230: 78475230
14 EDNRB NM_000115.4(EDNRB): c.914G> A (p.Ser305Asn) single nucleotide variant risk factor rs5352 GRCh38 Chromosome 13, 77901095: 77901095
15 MITF NM_000248.3(MITF): c.952G> A (p.Glu318Lys) single nucleotide variant risk factor rs149617956 GRCh37 Chromosome 3, 70014091: 70014091
16 MITF NM_000248.3(MITF): c.952G> A (p.Glu318Lys) single nucleotide variant risk factor rs149617956 GRCh38 Chromosome 3, 69964940: 69964940
17 MITF NM_198159.2(MITF): c.1190delG (p.Gly397Aspfs) deletion Pathogenic rs878853234 GRCh38 Chromosome 3, 69964875: 69964875
18 MITF NM_198159.2(MITF): c.1190delG (p.Gly397Aspfs) deletion Pathogenic rs878853234 GRCh37 Chromosome 3, 70014026: 70014026
19 MITF NM_000248.3(MITF): c.763C> T (p.Arg255Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1057517966 GRCh37 Chromosome 3, 70008476: 70008476
20 MITF NM_000248.3(MITF): c.763C> T (p.Arg255Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1057517966 GRCh38 Chromosome 3, 69959325: 69959325
21 MITF NM_000248.3(MITF): c.618G> C (p.Lys206Asn) single nucleotide variant Pathogenic rs1057519325 GRCh38 Chromosome 3, 69951870: 69951870
22 MITF NM_000248.3(MITF): c.618G> C (p.Lys206Asn) single nucleotide variant Pathogenic rs1057519325 GRCh37 Chromosome 3, 70001021: 70001021
23 MITF NM_000248.3(MITF): c.649A> G (p.Arg217Gly) single nucleotide variant Pathogenic rs1057519326 GRCh38 Chromosome 3, 69956469: 69956469
24 MITF NM_000248.3(MITF): c.649A> G (p.Arg217Gly) single nucleotide variant Pathogenic rs1057519326 GRCh37 Chromosome 3, 70005620: 70005620
25 MITF NM_000248.3(MITF): c.635-1G> A single nucleotide variant Pathogenic rs1057519327 GRCh38 Chromosome 3, 69956454: 69956454
26 MITF NM_000248.3(MITF): c.635-1G> A single nucleotide variant Pathogenic rs1057519327 GRCh37 Chromosome 3, 70005605: 70005605
27 MITF NM_198159.2(MITF): c.649C> T (p.Arg217Ter) single nucleotide variant Likely pathogenic GRCh38 Chromosome 3, 69939164: 69939164
28 MITF NM_198159.2(MITF): c.649C> T (p.Arg217Ter) single nucleotide variant Likely pathogenic GRCh37 Chromosome 3, 69988315: 69988315
29 SOX10 NM_006941.3(SOX10): c.1091delA (p.Gln364Argfs) deletion Likely pathogenic GRCh37 Chromosome 22, 38369812: 38369812
30 SOX10 NM_006941.3(SOX10): c.1091delA (p.Gln364Argfs) deletion Likely pathogenic GRCh38 Chromosome 22, 37973805: 37973805
31 SOX10 NM_006941.3(SOX10): c.430delC (p.Leu144Cysfs) deletion Likely pathogenic GRCh37 Chromosome 22, 38374141: 38374141
32 SOX10 NM_006941.3(SOX10): c.430delC (p.Leu144Cysfs) deletion Likely pathogenic GRCh38 Chromosome 22, 37978134: 37978134
33 SOX10 NM_006941.3(SOX10): c.403A> C (p.Ser135Arg) single nucleotide variant Likely pathogenic GRCh37 Chromosome 22, 38379389: 38379389
34 SOX10 NM_006941.3(SOX10): c.403A> C (p.Ser135Arg) single nucleotide variant Likely pathogenic GRCh38 Chromosome 22, 37983382: 37983382
35 SOX10 NM_006941.3(SOX10): c.44_62del19 (p.Val15Alafs) deletion Likely pathogenic GRCh38 Chromosome 22, 37983723: 37983741
36 SOX10 NM_006941.3(SOX10): c.44_62del19 (p.Val15Alafs) deletion Likely pathogenic GRCh37 Chromosome 22, 38379730: 38379748
37 MITF NM_000248.3(MITF): c.604G> A (p.Glu202Lys) single nucleotide variant Likely pathogenic GRCh37 Chromosome 3, 70001007: 70001007
38 MITF NM_000248.3(MITF): c.604G> A (p.Glu202Lys) single nucleotide variant Likely pathogenic GRCh38 Chromosome 3, 69951856: 69951856

Expression for Waardenburg Syndrome, Type 2a

Search GEO for disease gene expression data for Waardenburg Syndrome, Type 2a.

Pathways for Waardenburg Syndrome, Type 2a

Pathways related to Waardenburg Syndrome, Type 2a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.23 MITF TFE3
2 10.44 MITF TFE3

GO Terms for Waardenburg Syndrome, Type 2a

Biological processes related to Waardenburg Syndrome, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 humoral immune response GO:0006959 9.26 MITF TFE3
2 pigmentation GO:0043473 9.16 EDNRB MITF
3 melanocyte differentiation GO:0030318 8.96 EDNRB MITF
4 regulation of osteoclast differentiation GO:0045670 8.62 MITF TFE3

Molecular functions related to Waardenburg Syndrome, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.16 MITF TFE3
2 transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding GO:0001077 8.96 MITF TFE3
3 protein dimerization activity GO:0046983 8.62 MITF TFE3

Sources for Waardenburg Syndrome, Type 2a

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
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