Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: HELLS
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
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): HELLS .PanelApp HGNC gene symbol check: HELLS . IUIS Disease: Immunodeficiency with centromeric instability and facial anomalies, ICF4 . IUIS Inheritance: AR .T cells: Normal, .B cells: Decreased or normal, .IUIS Other affected cells: N/A. IUIS Associated features: Facial dysmorphic features, macroglossia, bacterial/opportunistic infections, malabsorption, cytopenias, malignancies, multiradial configurations of chromosomes 1, 9, 16. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: DNA Repair Defects other than those listed in Table 1Created: 2 Jul 2018, 10:35 a.m.
added tag-early-onsetCreated: 30 Apr 2018, 11:37 a.m.
Comment on list classification: Changed gene from status Amber to Green, there are more than three cases reported for immunodeficiency-centromeric instability-facial anomalies syndrome-4, all had immunoglobulin deficiency.Created: 26 Apr 2018, 2:06 p.m.
Comment on publications: added publications to support animal model - knockdown of the HELLS gene in mouse embryonic fibroblasts resulted in decreased CpG methylation at centromeric repeats, similar to that observed in patient cells.Created: 26 Apr 2018, 1:57 p.m.
From OMIM: PMID: 262163465 described patients from 4 unrelated families with immunodeficiency-centromeric instability-facial anomalies syndrome-4 , they identified 6 homozygous or compound heterozygous mutations in the HELLS gene. The mutations, which were found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the families. Only 1 of the mutations was a missense mutation. Functional studies of the variants were not performed, but knockdown of the HELLS gene in mouse embryonic fibroblasts resulted in decreased CpG methylation at centromeric repeats, similar to that observed in patient cells (PMID:11711429, 14517253,17726103, 16395332)Created: 26 Apr 2018, 1:56 p.m.
From Orphanet: disease characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes. Variable symptoms of this probably under-diagnosed syndrome include mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation. Serum levels of IgG, IgM, IgE, and/or IgA are low, although the type of immunoglobulin deficiency is variable. Recurrent infections are the presenting symptom, usually in early childhood.Created: 26 Apr 2018, 1:51 p.m.
Comment on mode of inheritance: MOI from review of literature and OMIMCreated: 26 Apr 2018, 1:23 p.m.
Comment on phenotypes: added phenotype and MIMid from OMIMCreated: 26 Apr 2018, 1:22 p.m.
Added from clinical team recommendation (Rachel Jones) after a literature review, to be curated thoroughly during panel review.Created: 10 Apr 2018, 8:31 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Immunodeficiency-centromeric instability-facial anomalies syndrome; ICF
Publications
Source NHS GMS was added to HELLS.
Source North West GLH was added to HELLS.
Source London North GLH was added to HELLS.
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.
Phenotypes for gene HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome, ICF, Immunodeficiency-centromeric instability-facial anomalies syndrome 4, 616911, ICF4, Facial dysmorphic features, macroglossia, bacterial/opportunistic infections, malabsorption, cytopenias, malignancies, multiradial configurations of chromosomes 1, 9, 16, Combined immunodeficiencies with associated or syndromic features
IUIS Classification February 2018 was added to HELLS. Panel: Primary immunodeficiency disorders
Gene: hells has been classified as Green List (High Evidence).
Phenotypes for HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome; ICF; Immunodeficiency-centromeric instability-facial anomalies syndrome 4, 616911; ICF4
This gene has been classified as Green List (High Evidence).
Publications for HELLS were set to 29339483; 28128455; 27328760; 26216346; 11711429; 14517253; 17726103; 16395332
Mode of inheritance for HELLS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome; ICF; Immunodeficiency-centromeric instability-facial anomalies syndrome 4, 616911
This gene has been classified as Amber List (Moderate Evidence).
HELLS was added to Primary immunodeficiency disorders panel. Sources: Literature
HELLS was created by Louise Daugherty