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Primary immunodeficiency

Gene: HELLS

Green List (high evidence)

HELLS (helicase, lymphoid specific)
EnsemblGeneIds (GRCh38): ENSG00000119969
EnsemblGeneIds (GRCh37): ENSG00000119969
OMIM: 603946, Gene2Phenotype
HELLS is in 3 panels

4 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

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 1
Created: 2 Jul 2018, 10:35 a.m.
added tag-early-onset
Created: 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 OMIM
Created: 26 Apr 2018, 1:23 p.m.
Comment on phenotypes: added phenotype and MIMid from OMIM
Created: 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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Expert Review Green
  • Literature
Phenotypes
  • 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
Tags
early-onset
OMIM
603946
Clinvar variants
Variants in HELLS
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to HELLS.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to HELLS.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to HELLS.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

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

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to HELLS. Panel: Primary immunodeficiency disorders

13 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: hells has been classified as Green List (High Evidence).

26 Apr 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome; ICF; Immunodeficiency-centromeric instability-facial anomalies syndrome 4, 616911; ICF4

26 Apr 2018, Gel status: 3

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

26 Apr 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for HELLS were set to 29339483; 28128455; 27328760; 26216346; 11711429; 14517253; 17726103; 16395332

26 Apr 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for HELLS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal

26 Apr 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome; ICF; Immunodeficiency-centromeric instability-facial anomalies syndrome 4, 616911

20 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

10 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

HELLS was added to Primary immunodeficiency disorders panel. Sources: Literature

10 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

HELLS was created by Louise Daugherty