Severe microcephaly

Gene: DIAPH1

Green List (high evidence)

DIAPH1 (diaphanous related formin 1)
EnsemblGeneIds (GRCh38): ENSG00000131504
EnsemblGeneIds (GRCh37): ENSG00000131504
OMIM: 602121, Gene2Phenotype
DIAPH1 is in 9 panels

2 reviews

Louise Daugherty (Genomics England Curator)

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green
Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Amber to Red based on advice from Adrianna Tucci: 3 unrelated human cases.
Created: 2 Mar 2017, 3:52 p.m.
Comment on list classification: Updated rating from Red to Amber: 3 separate cases of DIAPH1 mutations causing microcephaly, but reported mouse models don't exhibit microcephaly.
Created: 17 Jan 2017, 1:46 p.m.
3 cases reported in OMIM of DIAPH1 mutations linked to Seizures, cortical blindness, microcephaly syndrome (SCBMS, OMIM:616632) all from consanguineous Arab or Saudi Arabian parents. Note that mouse models don't exhibit microcephaly.
Created: 16 Jan 2017, 1:48 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • Literature
Phenotypes
  • microcephaly, blindness and early onset seizures
  • severe visual impairment, intellectual disability, and short stature
  • Seizures, cortical blindness, microcephaly syndrome, 616632
OMIM
602121
Clinvar variants
Variants in DIAPH1
Penetrance
Complete
Publications
  • 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

29 Jul 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to DIAPH1.

2 Mar 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.

2 Mar 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

17 Jan 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

16 Jan 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene DIAPH1 were set to microcephaly, blindness and early onset seizures; severe visual impairment, intellectual disability, and short stature; Seizures, cortical blindness, microcephaly syndrome, 616632

17 Feb 2016, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

DIAPH1 was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Literature

17 Feb 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

DIAPH1 was created by ellenmcdonagh