MCID: DFN036
MIFTS: 35

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 57 53 29 13 6
Nance Deafness 57 53 59 75
Dfnx2 57 53 59 75
Perilymphatic Gusher-Deafness Syndrome 57 53 75
Dfn3 57 53 75
Sensorineural Deafness, Profound, with or Without a Conductive Component, Associated with a Unique Developmental Abnormality of the Ear 57 53
X-Linked Mixed Conductive and Sensorineural Deafness 59 75
X-Linked Mixed Conductive and Neurosensory Deafness 59 75
Deafness 3 Conductive with Stapes Fixation 53 75
Deafness Conductive with Stapes Fixation 53 75
Deafness Mixed with Perilymphatic Gusher 53 75
Deafness X-Linked 2 with Non-Syndromic Mental Retardation 75
X-Linked Mixed Conductive and Sensorineural Hearing Loss 59
X-Linked Mixed Conductive and Neurosensory Hearing Loss 59
Deafness 3, Conductive, with Stapes Fixation; Dfn3 57
X-Linked Mixed Deafness with Perilymphatic Gusher 59
Deafness Mixed with Perilymph Gusher X-Linked 75
Deafness 3, Conductive, with Stapes Fixation 57
Dfn 3 Nonsyndromic Hearing Loss and Deafness 53
Deafness, Conductive, with Stapes Fixation 57
Deafness, Mixed, with Perilymphatic Gusher 57
Conductive Deafness with Stapes Fixation 59
Progressive Hearing Loss Stapes Fixation 73
X-Linked Stapes Gusher Syndrome 59
Deafness, X-Linked, Type 2 40
X-Linked Deafness Type 2 59
Deafness, X-Linked, 2 75
Gusher Syndrome 53

Characteristics:

Orphanet epidemiological data:

59
x-linked mixed deafness with perilymphatic gusher
Inheritance: X-linked recessive; Age of onset: Infancy; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
x-linked recessive

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


HPO:

32
deafness, x-linked 2:
Inheritance x-linked recessive inheritance


Classifications:



External Ids:

OMIM 57 304400
Orphanet 59 ORPHA383
ICD10 via Orphanet 34 H90.8
UMLS via Orphanet 74 C1844678
MeSH 44 D046089
SNOMED-CT via HPO 69 44057004
UMLS 73 C1844678

Summaries for Deafness, X-Linked 2

NIH Rare Diseases : 53 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.

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. 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 phenotypes are conductive hearing impairment and progressive sensorineural hearing impairment

OMIM : 57 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 : 75 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 38)
# 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 deafness, autosomal dominant 24 10.2 GJB2 GJB6
7 kid syndrome 10.2 GJB2 GJB6
8 pseudoainhum 10.2 GJB2 GJB6
9 congenital cytomegalovirus 10.1 GJB2 GJB6
10 knuckle pads, leukonychia, and sensorineural deafness 10.1 GJB2 GJB6
11 deafness, autosomal recessive 49 10.1 GJB2 POU3F4
12 hodgkin's lymphoma, nodular sclerosis 10.1 GJB2 GJB6
13 dfnb1 10.1 GJB2 GJB6
14 vohwinkel syndrome 10.1 GJB2 GJB6
15 deafness, autosomal recessive 1a 10.1 GJB2 GJB6
16 deafness, autosomal recessive 23 10.1 GJB2 GJB6
17 knuckle pads 10.1 GJB2 GJB6
18 non-syndromic genetic deafness 10.0 GJB2 POU3F4
19 vestibular disease 10.0 GJB2 GJB6
20 deafness, autosomal dominant 2a 10.0 GJB2 GJB6
21 deafness, autosomal recessive 16 10.0 GJB2 GJB6
22 erythrokeratodermia variabilis et progressiva 1 10.0 GJB2 GJB6
23 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
24 autosomal dominant non-syndromic sensorineural deafness type dfna 9.9 GJB2 GJB6
25 clouston syndrome 9.9 GJB2 GJB6
26 hereditary hearing loss and deafness 9.9 POU3F4 PRPS1
27 inner ear disease 9.9 GJB2 GJB6
28 charcot-marie-tooth disease, x-linked recessive, 5 9.9 POU3F4 PRPS1
29 keratitis, hereditary 9.8 GJB2 GJB6
30 x-linked nonsyndromic deafness 9.8 POU3F4 PRPS1
31 x-linked charcot-marie-tooth disease 9.8 GJB2 PRPS1
32 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 9.8 GJB2 GJB6
33 corneal disease 9.7 GJB2 GJB6
34 auditory system disease 9.6 GJB2 GJB6 POU3F4
35 sensorineural hearing loss 9.6 GJB2 GJB6 POU3F4
36 autosomal recessive non-syndromic sensorineural deafness type dfnb 9.6 GJB2 GJB6
37 nonsyndromic deafness 9.6 GJB2 GJB6 POU3F4
38 skin disease 9.3 GJB2 GJB6

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:

57
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:

32
# Description HPO Frequency HPO Source Accession
1 conductive hearing impairment 32 HP:0000405
2 progressive sensorineural hearing impairment 32 HP:0000408
3 stapes ankylosis 32 HP:0000381
4 dilatated internal auditory canal 32 HP:0004458

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

46
# 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 29 GJB2 GJB6 POU3F4

Anatomical Context for Deafness, X-Linked 2

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

41
Bone

Publications for Deafness, X-Linked 2

Articles related to Deafness, X-Linked 2:

# Title Authors Year
1
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:

75
# 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 44)
# Gene Variation Type Significance SNP ID Assembly Location
1 POU3F4 NM_000307.4(POU3F4): c.648delG (p.Leu217Trpfs) deletion Pathogenic GRCh38 Chromosome X, 83508972: 83508972
2 POU3F4 NM_000307.4(POU3F4): c.648delG (p.Leu217Trpfs) deletion Pathogenic GRCh37 Chromosome X, 82763980: 82763980
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.604A> T (p.Lys202Ter) single nucleotide variant Pathogenic rs104894920 GRCh38 Chromosome X, 83508928: 83508928
5 POU3F4 NM_000307.4(POU3F4): c.950T> G (p.Leu317Trp) single nucleotide variant Pathogenic rs104894921 GRCh37 Chromosome X, 82764282: 82764282
6 POU3F4 NM_000307.4(POU3F4): c.950T> G (p.Leu317Trp) single nucleotide variant Pathogenic rs104894921 GRCh38 Chromosome X, 83509274: 83509274
7 POU3F4 NM_000307.4(POU3F4): c.1000A> G (p.Lys334Glu) single nucleotide variant Pathogenic rs104894922 GRCh37 Chromosome X, 82764332: 82764332
8 POU3F4 NM_000307.4(POU3F4): c.1000A> G (p.Lys334Glu) single nucleotide variant Pathogenic rs104894922 GRCh38 Chromosome X, 83509324: 83509324
9 POU3F4 NM_000307.4(POU3F4): c.862_865delAGTG (p.Val289Argfs) deletion Pathogenic rs730882189 GRCh37 Chromosome X, 82764194: 82764197
10 POU3F4 NM_000307.4(POU3F4): c.862_865delAGTG (p.Val289Argfs) deletion Pathogenic rs730882189 GRCh38 Chromosome X, 83509186: 83509189
11 POU3F4 NM_000307.4(POU3F4): c.935C> T (p.Ala312Val) single nucleotide variant Pathogenic rs387906502 GRCh37 Chromosome X, 82764267: 82764267
12 POU3F4 NM_000307.4(POU3F4): c.935C> T (p.Ala312Val) single nucleotide variant Pathogenic rs387906502 GRCh38 Chromosome X, 83509259: 83509259
13 POU3F4 NM_000307.4(POU3F4): c.990A> T (p.Arg330Ser) single nucleotide variant Pathogenic rs104894923 GRCh37 Chromosome X, 82764322: 82764322
14 POU3F4 NM_000307.4(POU3F4): c.990A> T (p.Arg330Ser) single nucleotide variant Pathogenic rs104894923 GRCh38 Chromosome X, 83509314: 83509314
15 POU3F4 NM_000307.4(POU3F4): c.967C> G (p.Arg323Gly) single nucleotide variant Pathogenic rs104894924 GRCh37 Chromosome X, 82764299: 82764299
16 POU3F4 NM_000307.4(POU3F4): c.967C> G (p.Arg323Gly) single nucleotide variant Pathogenic rs104894924 GRCh38 Chromosome X, 83509291: 83509291
17 GJB2 NM_004004.5(GJB2): c.71G> A (p.Trp24Ter) single nucleotide variant Pathogenic rs104894396 GRCh37 Chromosome 13, 20763650: 20763650
18 GJB2 NM_004004.5(GJB2): c.71G> A (p.Trp24Ter) single nucleotide variant Pathogenic rs104894396 GRCh38 Chromosome 13, 20189511: 20189511
19 GJB2 NM_004004.5(GJB2): c.139G> T (p.Glu47Ter) single nucleotide variant Pathogenic rs104894398 GRCh37 Chromosome 13, 20763582: 20763582
20 GJB2 NM_004004.5(GJB2): c.139G> T (p.Glu47Ter) single nucleotide variant Pathogenic rs104894398 GRCh38 Chromosome 13, 20189443: 20189443
21 GJB2 NM_004004.5(GJB2): c.427C> T (p.Arg143Trp) single nucleotide variant Pathogenic rs80338948 GRCh37 Chromosome 13, 20763294: 20763294
22 GJB2 NM_004004.5(GJB2): c.427C> T (p.Arg143Trp) single nucleotide variant Pathogenic rs80338948 GRCh38 Chromosome 13, 20189155: 20189155
23 GJB2 NM_004004.5(GJB2): c.269T> C (p.Leu90Pro) single nucleotide variant Pathogenic rs80338945 GRCh37 Chromosome 13, 20763452: 20763452
24 GJB2 NM_004004.5(GJB2): c.269T> C (p.Leu90Pro) single nucleotide variant Pathogenic rs80338945 GRCh38 Chromosome 13, 20189313: 20189313
25 POU3F4 NM_000307.4(POU3F4): c.950dupT (p.Leu317Phefs) duplication Pathogenic rs398122516 GRCh37 Chromosome X, 82764282: 82764282
26 POU3F4 NM_000307.4(POU3F4): c.950dupT (p.Leu317Phefs) duplication Pathogenic rs398122516 GRCh38 Chromosome X, 83509274: 83509274
27 POU3F4 NM_000307.4(POU3F4): c.1060delA (p.Thr354Glnfs) deletion Pathogenic rs398122517 GRCh37 Chromosome X, 82764392: 82764392
28 POU3F4 NM_000307.4(POU3F4): c.1060delA (p.Thr354Glnfs) deletion Pathogenic rs398122517 GRCh38 Chromosome X, 83509384: 83509384
29 GJB2 NM_004004.5(GJB2): c.283G> A (p.Val95Met) single nucleotide variant Pathogenic/Likely pathogenic rs111033299 GRCh37 Chromosome 13, 20763438: 20763438
30 GJB2 NM_004004.5(GJB2): c.283G> A (p.Val95Met) single nucleotide variant Pathogenic/Likely pathogenic rs111033299 GRCh38 Chromosome 13, 20189299: 20189299
31 GJB2 NM_004004.5(GJB2): c.416G> A (p.Ser139Asn) single nucleotide variant Pathogenic/Likely pathogenic rs76434661 GRCh37 Chromosome 13, 20763305: 20763305
32 GJB2 NM_004004.5(GJB2): c.416G> A (p.Ser139Asn) single nucleotide variant Pathogenic/Likely pathogenic rs76434661 GRCh38 Chromosome 13, 20189166: 20189166
33 GJB2 NM_004004.5(GJB2): c.617A> G (p.Asn206Ser) single nucleotide variant Pathogenic rs111033294 GRCh37 Chromosome 13, 20763104: 20763104
34 GJB2 NM_004004.5(GJB2): c.617A> G (p.Asn206Ser) single nucleotide variant Pathogenic rs111033294 GRCh38 Chromosome 13, 20188965: 20188965
35 POU3F4 NM_000307.4(POU3F4): c.896delA (p.Lys299Serfs) deletion Pathogenic rs267606974 GRCh37 Chromosome X, 82764227: 82764227
36 POU3F4 NM_000307.4(POU3F4): c.896delA (p.Lys299Serfs) deletion Pathogenic rs267606974 GRCh38 Chromosome X, 83509220: 83509220
37 GJB2 NM_004004.5(GJB2): c.131G> A (p.Trp44Ter) single nucleotide variant Pathogenic/Likely pathogenic rs104894413 GRCh38 Chromosome 13, 20189451: 20189451
38 GJB2 NM_004004.5(GJB2): c.131G> A (p.Trp44Ter) single nucleotide variant Pathogenic/Likely pathogenic rs104894413 GRCh37 Chromosome 13, 20763590: 20763590
39 POU3F4 NM_000307.4(POU3F4): c.235C> T (p.Gln79Ter) single nucleotide variant Pathogenic rs878853242 GRCh38 Chromosome X, 83508559: 83508559
40 POU3F4 NM_000307.4(POU3F4): c.235C> T (p.Gln79Ter) single nucleotide variant Pathogenic rs878853242 GRCh37 Chromosome X, 82763567: 82763567
41 POU3F4 NM_000307.4(POU3F4): c.845G> T (p.Arg282Leu) single nucleotide variant Uncertain significance rs1060499806 GRCh38 Chromosome X, 83509169: 83509169
42 POU3F4 NM_000307.4(POU3F4): c.845G> T (p.Arg282Leu) single nucleotide variant Uncertain significance rs1060499806 GRCh37 Chromosome X, 82764177: 82764177
43 POU3F4 NM_000307.4(POU3F4): c.877C> G (p.Leu293Val) single nucleotide variant Pathogenic rs780027419 GRCh37 Chromosome X, 82764209: 82764209
44 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
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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