Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: UNC93B1
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on list classification: 3 unrelated cases with plausible disease causing mutations.Created: 21 Jun 2018, 2:44 p.m.
Comment on phenotypes: Added OMIM phenotypeCreated: 21 Jun 2018, 2:34 p.m.
Comment on publications: Added relevant publicationsCreated: 21 Jun 2018, 2:21 p.m.
In OMIM UNC93B1 is associated with {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1}. OMIM evidence comes from Casrouge et al. (2006) (PMID: 16973841) who reports 2 individuals with herpes simplex encephalitis (HSE) caused by deficiency of UNC93B1. Both patients were the products of consanguineous unions. One patient was homozygous for a frameshift mutation resulting in barely detectable UNC93B1 RNA. The other was homozygous for a splice site mutation at the end of exon 6 resulting in skipping of exon 6 of UNC93B1. Neither of these variants were identified in 100 healthy European controls. Feng et al 2015 (PMID: 26757972) report a Chinese patient homozygous for a single-nucleotide substitution at position C.414C>G in exon 4 of UNC93B1 which affected the expression of UNC93B1. PubMed, Clinvar and JensenLab Disease (https://diseases.jensenlab.org/) searches have not found published studies of further cases. No pathogenic variants reported in ClinVar. A mouse model with a missense allele of Unc93b1 exists (Tabeta et al. (2006)(PMID: 16415873) and functional studies show the role of UNC93B1 in regulating Toll-like receptors that play a key role in the innate immune system e.g. Pelka et al. 2018 (PMID: 29768176).Created: 21 Jun 2018, 2:19 p.m.
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): UNC93B1 .PanelApp HGNC gene symbol check: UNC93B1 . IUIS Disease: UNC93B1 deficiency . IUIS Inheritance: AR , .B cells: N/A, .IUIS Other affected cells: CNS resident cells and fibroblasts. IUIS Associated features: Herpes simplex virus 1 encephalitis. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Herpes Simplex Encephalitis (HSE)Created: 2 Jul 2018, 10:35 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s)
GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 19 Apr 2018, 10:49 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: UNC93, PanelApp HGNC gene symbol check: UNC93B1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Herpetic encephalitis / Herpetic encephalitis (HSE)Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: UNC93B1, GRID_Gene_Symbol: UNC93B1, GRID_Transcript_ENS_Community submitted: ENST00000227471, GRID_Transcript_RefSeq: NM_030930.2, GRID_Transcript_ENS_used_on_Production: ENST00000227471Created: 17 Apr 2018, 12:12 p.m.
Source NHS GMS was added to UNC93B1.
Source North West GLH was added to UNC93B1.
Source London North GLH was added to UNC93B1.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Gene: unc93b1 has been classified as Green List (High Evidence).
Phenotypes for gene UNC93B1 were set to Herpes simplex encephalitis, susceptibility to, 1, Herpetic encephalitis (HSE), {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1} 610551, Herpes simplex virus 1 encephalitis, Defects in Intrinsic and Innate Immunity
IUIS Classification February 2018 was added to UNC93B1. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to UNC93B1. Panel: Primary immunodeficiency disorders
Gene: unc93b1 has been classified as Green List (High Evidence).
Phenotypes for gene: UNC93B1 were set to Herpes simplex encephalitis, susceptibility to, 1; Herpetic encephalitis (HSE); {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 1} 610551
Publications for gene: UNC93B1 were set to 16973841; 16415873; 29768176
This gene has been classified as Amber List (Moderate Evidence).
ESID Registry 20171117 was added to UNC93B1. Panel: Primary immunodeficiency disorders Phenotypes for gene UNC93B1 were set to Herpes simplex encephalitis, susceptibility to, 1, Herpetic encephalitis (HSE)
Phenotypes for gene UNC93B1 were set to Herpes simplex encephalitis, susceptibility to, 1
UNC93B1 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
UNC93B1 was created by Louise Daugherty