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Hearing loss

Gene: DIAPH3

Amber List (moderate evidence)

DIAPH3 (diaphanous related formin 3)
EnsemblGeneIds (GRCh38): ENSG00000139734
EnsemblGeneIds (GRCh37): ENSG00000139734
OMIM: 614567, Gene2Phenotype
DIAPH3 is in 2 panels

5 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Changing the rating from red to amber as there are now 2 reported cases.
Created: 17 Feb 2019, 11:26 p.m.
Associated with Auditory neuropathy, autosomal dominant, 1 (609129) in OMIM.

PMID: 20624953 - Schoen et al. (2010) - Identified a heterozygous mutation (-172G-A) in the 5-prime untranslated region of the DIAPH3 gene in a large family (33 affected members) with autosomal dominant auditory neuropathy-1. Some individuals are homozygous for the variant. Using genome-wide expression arrays and quantitative RT-PCR, they demonstrate a 2- to 3-fold overexpression of DIAPH3 mRNA in lymphoblastoid cell lines from affected individuals.

PMID: 27658576 - Martinez et al 2017 - 3 family members with progressive bilateral deafness from the age of 20 years. A c.-173C>T variant, located in the regulatory region of DIAPH3 was found in affected family members, but not in 2 unaffected family members.
Created: 17 Feb 2019, 11:25 p.m.

Emma Ashton (Great Ormond Street Hospital)

Green List (high evidence)

HGMD c.-172G>A c.-173C>T both pathogenic (Schoen et al 2010 PMID 20624953; Sanchez-Martinez et al 2017 PMID 27658576). Two separate families, 3 affected members have c.-173C>T, 2 unaffected members dont. c.-172G>A v large 4 generation pedigree inc 33 affected family members. Quantitative RT-PCR shows 2-3 fold overexpression of DIAPH3 mRNA in lymphoblastoid cell lines from affected individuals.
Created: 17 Feb 2019, 4:35 p.m.

Publications

Maria Bitner-Glindzicz (UCL)

Red List (low evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
auditory neuropathy

Publications

Mode of pathogenicity
Other

Ellen McDonagh (Genomics England Curator)

Comment on mode of inheritance: PMID: 20624953 identifies both heterozygotes and homozygotes of the 5'UTR variant they describe with an association with auditory neuropathy.
Created: 23 Feb 2016, 10:45 a.m.
Comment on mode of pathogenicity: PubMed: 20624953 describes a gain-of-function mechanism resulting from the 5'UTR variant.
Created: 23 Feb 2016, 10:44 a.m.
Comment on list classification: Demoted from amber to red. Reported in one family - more evidence required.
Created: 23 Feb 2016, 10:32 a.m.

Jun Shen (Harvard Medical School)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
#609129:Auditory neuropathy, autosomal dominant, 1[Hearing loss, neural typeAbnormal or absent auditory nerve and brainstem responsesAbsent middle ear reflexesAbnormal auditory temporal processesAbnormal gap detectionAbnormal amplitude modulation detectionAbnormal speech discriminationNormal outer hair cell functionsNormal otoacoustic emissionsNormal cochlear microphonics]

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Auditory neuropathy, autosomal dominant, 1, 609129
OMIM
614567
Clinvar variants
Variants in DIAPH3
Penetrance
Complete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

17 Feb 2019, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: DIAPH3 were set to PMID: 14767582; 15520414; 18755006; 19457867; 20624953

17 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: diaph3 has been classified as Amber List (Moderate Evidence).

23 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

23 Feb 2016, Gel status: 1

Set mode of pathogenicity

Ellen McDonagh (Genomics England Curator)

Mode of pathogenicity for DIAPH3 was changed to Other - please provide details in the comments

23 Feb 2016, Gel status: 1

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for DIAPH3 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

23 Feb 2016, Gel status: 1

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for DIAPH3 were set to Auditory neuropathy, autosomal dominant, 1, 609129

23 Feb 2016, Gel status: 1

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for DIAPH3 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

23 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

23 Feb 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for DIAPH3 were set to PMID: 14767582; 15520414; 18755006; 19457867; 20624953

23 Feb 2016, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for DIAPH3 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

24 Jun 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH3 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Radboud University Medical Center, Nijmegen

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH3 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Radboud University Medical Center, Nijmegen