Genes in panel
STRs in panel
Prev Next
Regions in panel
Prev Next

Hearing loss

Gene: DIAPH1

Green List (high evidence)

DIAPH1 (diaphanous related formin 1)
EnsemblGeneIds (GRCh38): ENSG00000131504
EnsemblGeneIds (GRCh37): ENSG00000131504
OMIM: 602121, Gene2Phenotype
DIAPH1 is in 10 panels

5 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Upgrading from red to green after discussion with the GMS hearing loss specialist test group in a Webex and consultation with the Genomics England clinical team
Created: 12 Jun 2019, 11:20 a.m. | Last Modified: 14 Aug 2019, 9:39 a.m.
Panel Version: 1.122
DIAPH1 has a previous gene symbol of DFNA1.
It is associated with Deafness, autosomal dominant 1 (124900) in OMIM

PMID: 9360932 - Lynch et al 1997 - a splice donor mutation in the penultimate exon of the DIAPH1 gene was identified in affected members of a large Costa Rican kindred with autosomal dominant deafness-1

PMID: 26912466 - Stritt et al. 2016 - a heterozygous truncating mutation in the DIAPH1 gene (R1213X) was identified in 8 affected individuals from 2 unrelated families with macrothrombocytopenia and sensorineural hearing loss. It segregated with the disorder in both families. R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was linked to reduced proplatelet formation from cultured MKs, cell clustering, and abnormal cortical filamentous actin. In platelets, there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. The authors suggest this is a gain-of-function action.

PMID: 27808407 - Neuhaus et al. (2017) identified two new DFNA1 families with thrombocytopenia as an associated finding each with a heterozygous truncating mutation DIAPH1 gene, (c.3637C>T, p.Arg1213* and a 2-bp deletion c.3624_3625delAG (p.Ala1210Serfs*31).
Created: 18 Feb 2019, 11:04 p.m.

Emma Ashton (Great Ormond Street Hospital)

Green List (high evidence)

6 DM variants associated with hearing loss on HGMD, multiple publications. Also pathogenic variants reported in association with microcephaly. OMIM AD deafness 1 #124900. AR variants associated with seizures, cortical blindness microcephaly syndrome #616632
Created: 17 Feb 2019, 4:35 p.m.

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Evidence for causing deafness has been found in only one family, therefore this should be demoted from green to red.
Created: 23 Feb 2016, 10:20 a.m.
PMID: 1350680 and 9360932 - original studies mapping the cause of autosomal dominant nonsyndromic deafness in the Cost Rican M Kindred to a region on chromosome 5q31 named the DFNA1 gene. All 78 affected members were heterozygous for a mutation found within the gene that caused abberant splicing; PMID: 24781755 - a family study identify a homozygous nonsense alteration as the cause of microcephaly (MCP), severe visual impairment, intellectual disability, and short stature; PMID: 26463574 - describes a case of an affected boy from United Arab Emirates, and a seperate family with 3 affected siblings of Omani ancestry, and identify likely causative homozygous variants in this gene in the individuals affected with microcephaly, blindness and early onset seizures.
Created: 17 Feb 2016, 2:20 p.m.
Comment on list classification: Only one family study for autosomal dominant deafness has been reported. 3 family cases for the association between biallelic mutations and microcephaly, cortical blindness and seizures (and not deafness).
Created: 17 Feb 2016, 2:18 p.m.

Jun Shen (Harvard Medical School)

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
#124900:Deafness, autosomal dominant 1[Sensorineural hearing loss; Progressive hearing loss; Low-frequency hearing loss; Childhood onset]; #616632:Seizures, cortical blindness, microcephaly syndrome[Short stature; Poor growth; Microcephaly (up to -10 SD); Cortical blindnessOptic atrophy; Hypotonia (in some patients); Delayed psychomotor development, moderate to severeSeizuresPoor speechHypoplasia of the corpus callosum]

Publications

Maria Bitner-Glindzicz (UCL)

I don't know

Only one convincing family published
Created: 30 Sep 2015, 1:24 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • Nonsyndromic Hearing Loss, Mixed
  • Deafness, autosomal dominant 1, 124900
  • hearing loss
OMIM
602121
Clinvar variants
Variants in DIAPH1
Penetrance
Complete
Publications
  • PMID:12021256
  • 12034774
  • 15864301
  • 17182868
  • 24781755
  • PMID: 1350680 and 9360932 - original studies mapping the cause of autosomal dominant nonsyndromic deafness in the Cost Rican M Kindred to a region on chromosome 5q31 named the DFNA1 gene. All 78 affected members were heterozygous for a mutation found within the gene that caused abberant splicing
  • PMID: 24781755 - a family study identify a homozygous nonsense alteration as the cause of microcephaly (MCP), severe visual impairment, intellectual disability, and short stature
  • PMID: 26463574 - describes a case of an affected boy from United Arab Emirates, and a seperate family with 3 affected siblings of Omani ancestry, and identify likely causative homozygous variants in this gene in the individuals affected with microcephaly, blindness and early onset seizures.
Panels with this gene

History Filter Activity

12 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: diaph1 has been classified as Green List (High 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

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

17 Feb 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for DIAPH1 were set to PMID:12021256; 12034774; 15864301; 17182868; 24781755; PMID: 1350680 and 9360932 - original studies mapping the cause of autosomal dominant nonsyndromic deafness in the Cost Rican M Kindred to a region on chromosome 5q31 named the DFNA1 gene. All 78 affected members were heterozygous for a mutation found within the gene that caused abberant splicing; PMID: 24781755 - a family study identify a homozygous nonsense alteration as the cause of microcephaly (MCP), severe visual impairment, intellectual disability, and short stature; PMID: 26463574 - describes a case of an affected boy from United Arab Emirates, and a seperate family with 3 affected siblings of Omani ancestry, and identify likely causative homozygous variants in this gene in the individuals affected with microcephaly, blindness and early onset seizures.

17 Feb 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for DIAPH1 were set to PMID:12021256; 12034774; 15864301; 17182868; 24781755; 9360932

17 Feb 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

24 Jun 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene DIAPH1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene DIAPH1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene DIAPH1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene DIAPH1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

24 Jun 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: UKGTN,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert