MCID: DFN036
MIFTS: 36

Deafness, X-Linked 2

Categories: Genetic diseases, Rare diseases, Ear diseases, Neuronal diseases, Mental diseases

Aliases & Classifications for Deafness, X-Linked 2

MalaCards integrated aliases for Deafness, X-Linked 2:

Name: Deafness, X-Linked 2 53 49 28 13
Nance Deafness 53 49 55 71
Dfnx2 53 49 55 71
Perilymphatic Gusher-Deafness Syndrome 53 49 71
Dfn3 53 49 71
Sensorineural Deafness, Profound, with or Without a Conductive Component, Associated with a Unique Developmental Abnormality of the Ear 53 49
X-Linked Mixed Conductive and Sensorineural Deafness 55 71
X-Linked Mixed Conductive and Neurosensory Deafness 55 71
Deafness 3 Conductive with Stapes Fixation 49 71
Deafness Conductive with Stapes Fixation 49 71
Deafness Mixed with Perilymphatic Gusher 49 71
Deafness X-Linked 2 with Non-Syndromic Mental Retardation 71
X-Linked Mixed Conductive and Sensorineural Hearing Loss 55
X-Linked Mixed Conductive and Neurosensory Hearing Loss 55
Deafness 3, Conductive, with Stapes Fixation; Dfn3 53
X-Linked Mixed Deafness with Perilymphatic Gusher 55
Deafness Mixed with Perilymph Gusher X-Linked 71
Deafness 3, Conductive, with Stapes Fixation 53
Dfn 3 Nonsyndromic Hearing Loss and Deafness 49
Deafness, Conductive, with Stapes Fixation 53
Deafness, Mixed, with Perilymphatic Gusher 53
Conductive Deafness with Stapes Fixation 55
Progressive Hearing Loss Stapes Fixation 69
X-Linked Stapes Gusher Syndrome 55
X-Linked Deafness Type 2 55
Deafness, X-Linked, 2 71
Gusher Syndrome 49

Characteristics:

Orphanet epidemiological data:

55
x-linked mixed deafness with perilymphatic gusher
Inheritance: X-linked recessive; Age of onset: Infancy; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
x-linked recessive

Miscellaneous:
leakage of fluid ('gusher') if the stapes is disturbed
female carriers may have mild hearing impairment


HPO:

31
deafness, x-linked 2:
Inheritance x-linked recessive inheritance


Classifications:



External Ids:

OMIM 53 304400
Orphanet 55 ORPHA383
UMLS via Orphanet 70 C1844678
ICD10 via Orphanet 33 H90.8
MeSH 41 D046089
SNOMED-CT via HPO 65 44057004
UMLS 69 C1844678

Summaries for Deafness, X-Linked 2

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 383Disease definitionX-linked mixed deafness with perilymphatic gusher, also known as X-linked deafness type 2, is a rare form of non-syndromic genetic deafnesss affecting males and characterized by pathognomonic inner ear anomalies and conductive and profound sensorineural hearing loss. The inner ear anomalies are described as dilatation of the internal auditory meatus and fistulous connection between the cochlear basal turn and internal auditory canal resulting in perilympatic gusher on attempted mobilization of a fixed stapes. Obligate female carriers may suffer from mild to moderate hearing loss.Visit the Orphanet disease page for more resources. Last updated: 5/22/2015

MalaCards based summary : Deafness, X-Linked 2, also known as nance deafness, is related to deafness mixed with perilymphatic gusher, x-linked and deafness x-linked, dfn3, and has symptoms including conductive hearing impairment, progressive sensorineural hearing impairment and stapes ankylosis. An important gene associated with Deafness, X-Linked 2 is POU3F4 (POU Class 3 Homeobox 4), and among its related pathways/superpathways is Gap junction trafficking. Affiliated tissues include bone, and related phenotype is hearing/vestibular/ear.

OMIM : 53 DFNX2, also known as DFN3, is an X-linked recessive disorder characterized by progressive conductive and sensorineural hearing loss and a pathognomonic temporal bone deformity that includes dilatation of the inner auditory canal and a fistulous connection between the internal auditory canal and the cochlear basal turn, resulting in a perilymphatic fluid 'gusher' during stapes surgery (summary by de Kok et al., 1995 and Song et al., 2010). See also choroideremia, deafness, and mental retardation (303110), a contiguous gene deletion syndrome involving the POU3F4 and CHM (300390) genes on Xq21; isolated choroideremia (303100) is caused by mutation in the CHM gene. (304400)

UniProtKB/Swiss-Prot : 71 Deafness, X-linked, 2: A form of deafness characterized by both conductive hearing loss resulting from stapes (perilymphatic gusher) fixation, and progressive sensorineural deafness.

Related Diseases for Deafness, X-Linked 2

Diseases in the X-Linked Nonsyndromic Deafness family:

Deafness, X-Linked 3 Deafness, X-Linked 4
Deafness, X-Linked 5 Deafness, X-Linked 6
Deafness, X-Linked 2 Deafness, X-Linked 1
Deafness, Y-Linked 1

Diseases related to Deafness, X-Linked 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 41)
# Related Disease Score Top Affiliating Genes
1 deafness mixed with perilymphatic gusher, x-linked 12.4
2 deafness x-linked, dfn3 11.9
3 deafness, x-linked 1 11.4
4 deafness-hypogonadism syndrome 11.1
5 choroideremia 10.9
6 hereditary hearing loss and deafness 10.0 POU3F4 PRPS1
7 x-linked nonsyndromic deafness 10.0 POU3F4 PRPS1
8 charcot-marie-tooth disease, x-linked recessive, 5 10.0 POU3F4 PRPS1
9 branchiootic syndrome 1 9.9
10 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
11 deafness, autosomal recessive 1b 9.9 GJB2 GJB6
12 deafness, autosomal dominant 24 9.9 GJB2 GJB6
13 kid syndrome 9.9 GJB2 GJB6
14 pseudoainhum 9.9 GJB2 GJB6
15 knuckle pads, leukonychia, and sensorineural deafness 9.9 GJB2 GJB6
16 deafness, autosomal recessive 1a 9.9 GJB2 GJB6
17 congenital cytomegalovirus 9.8 GJB2 GJB6
18 hodgkin's lymphoma, nodular sclerosis 9.8 GJB2 GJB6
19 dfnb1 9.8 GJB2 GJB6
20 vohwinkel syndrome 9.8 GJB2 GJB6
21 knuckle pads 9.8 GJB2 GJB6
22 deafness, autosomal recessive 49 9.8 GJB2 POU3F4
23 vestibular disease 9.8 GJB2 GJB6
24 deafness, autosomal recessive 16 9.8 GJB2 GJB6
25 deafness, autosomal dominant 2a 9.8 GJB2 GJB6
26 x-linked charcot-marie-tooth disease 9.8 GJB2 PRPS1
27 erythrokeratodermia variabilis et progressiva 1 9.8 GJB2 GJB6
28 autosomal dominant non-syndromic sensorineural deafness type dfna 9.8 GJB2 GJB6
29 clouston syndrome 9.8 GJB2 GJB6
30 deafness, autosomal recessive 12 9.7 GJB2 GJB6
31 inner ear disease 9.7 GJB2 GJB6
32 keratitis, hereditary 9.7 GJB2 GJB6
33 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 9.7 GJB2 GJB6
34 corneal disease 9.7 GJB2 GJB6
35 autosomal recessive non-syndromic sensorineural deafness type dfnb 9.6 GJB2 GJB6
36 sensorineural hearing loss 9.6 GJB2 GJB6
37 skin disease 9.5 GJB2 GJB6
38 non-syndromic genetic deafness 9.5 GJB2 GJB6 POU3F4
39 auditory system disease 9.5 GJB2 GJB6 POU3F4
40 nonsyndromic deafness 9.5 GJB2 GJB6 POU3F4
41 retinitis pigmentosa 8.9 GJB2 GJB6 PRPS1

Graphical network of the top 20 diseases related to Deafness, X-Linked 2:



Diseases related to Deafness, X-Linked 2

Symptoms & Phenotypes for Deafness, X-Linked 2

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Ears:
deafness, profound
hearing loss, conductive
hearing loss, sensorineural, progressive
wide bulbous internal auditory meatus
deficient or absent bone between the lateral end of the meatus and basal turn of the cochlea
more

Clinical features from OMIM:

304400

Human phenotypes related to Deafness, X-Linked 2:

31
# Description HPO Frequency HPO Source Accession
1 conductive hearing impairment 31 HP:0000405
2 progressive sensorineural hearing impairment 31 HP:0000408
3 stapes ankylosis 31 HP:0000381
4 dilatated internal auditory canal 31 HP:0004458

MGI Mouse Phenotypes related to Deafness, X-Linked 2:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.8 GJB2 GJB6 POU3F4

Drugs & Therapeutics for Deafness, X-Linked 2

Search Clinical Trials , NIH Clinical Center for Deafness, X-Linked 2

Genetic Tests for Deafness, X-Linked 2

Genetic tests related to Deafness, X-Linked 2:

# Genetic test Affiliating Genes
1 Deafness, X-Linked 2 28 GJB2 GJB6 POU3F4

Anatomical Context for Deafness, X-Linked 2

MalaCards organs/tissues related to Deafness, X-Linked 2:

38
Bone

Publications for Deafness, X-Linked 2

Articles related to Deafness, X-Linked 2:

# Title Authors Year
1
Audiological and surgical evidence for the presence of a third window effect for the conductive hearing loss in DFNX2 deafness irrespective of types of mutations. ( 23400403 )
2013
2
Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher. ( 9109724 )
1997

Variations for Deafness, X-Linked 2

UniProtKB/Swiss-Prot genetic disease variations for Deafness, X-Linked 2:

71
# Symbol AA change Variation ID SNP ID
1 POU3F4 p.Ala312Val VAR_003782
2 POU3F4 p.Leu317Trp VAR_003783
3 POU3F4 p.Arg323Gly VAR_003784
4 POU3F4 p.Arg330Ser VAR_003785
5 POU3F4 p.Lys334Glu VAR_003786

ClinVar genetic disease variations for Deafness, X-Linked 2:

6 (show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 POU3F4 NM_000307.4(POU3F4): c.967C> G (p.Arg323Gly) single nucleotide variant Pathogenic rs104894924 GRCh38 Chromosome X, 83509291: 83509291
2 POU3F4 POU3F4, ASP215TER undetermined variant Pathogenic
3 POU3F4 NM_000307.4(POU3F4): c.604A> T (p.Lys202Ter) single nucleotide variant Pathogenic rs104894920 GRCh37 Chromosome X, 82763936: 82763936
4 POU3F4 NM_000307.4(POU3F4): c.950T> G (p.Leu317Trp) single nucleotide variant Pathogenic rs104894921 GRCh37 Chromosome X, 82764282: 82764282
5 POU3F4 NM_000307.4(POU3F4): c.1000A> G (p.Lys334Glu) single nucleotide variant Pathogenic rs104894922 GRCh37 Chromosome X, 82764332: 82764332
6 POU3F4 NM_000307.4(POU3F4): c.862_865delAGTG (p.Val289Argfs) deletion Pathogenic rs730882189 GRCh37 Chromosome X, 82764194: 82764197
7 POU3F4 NM_000307.4(POU3F4): c.935C> T (p.Ala312Val) single nucleotide variant Pathogenic rs387906502 GRCh37 Chromosome X, 82764267: 82764267
8 POU3F4 NM_000307.4(POU3F4): c.990A> T (p.Arg330Ser) single nucleotide variant Pathogenic rs104894923 GRCh37 Chromosome X, 82764322: 82764322
9 GJB2 NM_004004.5(GJB2): c.71G> A (p.Trp24Ter) single nucleotide variant Pathogenic rs104894396 GRCh37 Chromosome 13, 20763650: 20763650
10 GJB2 NM_004004.5(GJB2): c.139G> T (p.Glu47Ter) single nucleotide variant Pathogenic rs104894398 GRCh37 Chromosome 13, 20763582: 20763582
11 GJB2 NM_004004.5(GJB2): c.427C> T (p.Arg143Trp) single nucleotide variant Pathogenic rs80338948 GRCh37 Chromosome 13, 20763294: 20763294
12 GJB2 NM_004004.5(GJB2): c.269T> C (p.Leu90Pro) single nucleotide variant Pathogenic rs80338945 GRCh37 Chromosome 13, 20763452: 20763452
13 POU3F4 NM_000307.4(POU3F4): c.950dupT (p.Leu317Phefs) duplication Pathogenic rs398122516 GRCh37 Chromosome X, 82764282: 82764282
14 POU3F4 NM_000307.4(POU3F4): c.1060delA (p.Thr354Glnfs) deletion Pathogenic rs398122517 GRCh37 Chromosome X, 82764392: 82764392
15 GJB2 NM_004004.5(GJB2): c.283G> A (p.Val95Met) single nucleotide variant Pathogenic/Likely pathogenic rs111033299 GRCh37 Chromosome 13, 20763438: 20763438
16 GJB2 NM_004004.5(GJB2): c.416G> A (p.Ser139Asn) single nucleotide variant Pathogenic/Likely pathogenic rs76434661 GRCh37 Chromosome 13, 20763305: 20763305
17 GJB2 NM_004004.5(GJB2): c.617A> G (p.Asn206Ser) single nucleotide variant Pathogenic rs111033294 GRCh37 Chromosome 13, 20763104: 20763104
18 POU3F4 NM_000307.4(POU3F4): c.896delA (p.Lys299Serfs) deletion Pathogenic rs267606974 GRCh37 Chromosome X, 82764227: 82764227
19 GJB2 NM_004004.5(GJB2): c.131G> A (p.Trp44Ter) single nucleotide variant Pathogenic/Likely pathogenic rs104894413 GRCh37 Chromosome 13, 20763590: 20763590
20 POU3F4 NM_000307.4(POU3F4): c.235C> T (p.Gln79Ter) single nucleotide variant Pathogenic rs878853242 GRCh38 Chromosome X, 83508559: 83508559
21 POU3F4 NM_000307.4(POU3F4): c.845G> T (p.Arg282Leu) single nucleotide variant Pathogenic rs1060499806 GRCh38 Chromosome X, 83509169: 83509169
22 POU3F4 NM_000307.4(POU3F4): c.877C> G (p.Leu293Val) single nucleotide variant Pathogenic rs780027419 GRCh38 Chromosome X, 83509201: 83509201

Expression for Deafness, X-Linked 2

Search GEO for disease gene expression data for Deafness, X-Linked 2.

Pathways for Deafness, X-Linked 2

Pathways related to Deafness, X-Linked 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.61 GJB2 GJB6

GO Terms for Deafness, X-Linked 2

Cellular components related to Deafness, X-Linked 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 gap junction GO:0005921 8.96 GJB2 GJB6
2 connexin complex GO:0005922 8.62 GJB2 GJB6

Biological processes related to Deafness, X-Linked 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 response to lipopolysaccharide GO:0032496 9.32 GJB2 GJB6
2 aging GO:0007568 9.26 GJB2 GJB6
3 cell communication GO:0007154 9.16 GJB2 GJB6
4 sensory perception of sound GO:0007605 9.13 GJB2 GJB6 POU3F4
5 inner ear development GO:0048839 8.8 GJB2 GJB6 POU3F4

Sources for Deafness, X-Linked 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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