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Primary immunodeficiency

Gene: SPINK5

Green List (high evidence)

SPINK5 (serine peptidase inhibitor, Kazal type 5)
EnsemblGeneIds (GRCh38): ENSG00000133710
EnsemblGeneIds (GRCh37): ENSG00000133710
OMIM: 605010, Gene2Phenotype
SPINK5 is in 9 panels

6 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)

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: MIM number added to Netherton syndrome phenotype
Created: 16 May 2018, 1:55 p.m.
Comment on list classification: Rating this gene as green as there are more than 3 cases of plausable pathogenic mutations.
Created: 16 May 2018, 1:47 p.m.
In OMIM SPINK5 is associated with Netherton syndrome, a skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. It has been defined as a primary immunodeficiency by Renner et al 2009 (PMID: 19683336 ). Evidence in OMIM that SPINK5 is causative of Netherton syndrome comes from the publication of Chavanas et al. (2000) (PMID: 10835624) who report that among 13 families segregating Netherton syndrome, 11 different mutations in the SPINK5 gene were detected, at least 9 of which generated premature termination codons and predicted mRNA instability. From a PubMed search, Renner et al 2009 reports the analysis of 9 unrelated patients. All, except one, had mutations in SPINK5. 6 novel variants were identified. Most mutations result in a frame shift and early termination of translation. Of the four intronic mutations, three were found at highly conserved intron-exon boundaries. Other cases are described in Nevet et al 2017 (PMID: 28832989), Shi et al 2017 (PMID: 28943498) (along with a variant in FLG), Śmigiel R et al 2017 (PMID: 28289593) among others.
Rating this gene as green as there are more than 3 cases of plausable pathogenic mutations.
Created: 16 May 2018, 1:45 p.m.
Added the tag of early onset as features of Netherton syndrome are apparent at or soon after birth.
Created: 16 May 2018, 1 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Ellen McDonagh (Genomics England Curator)

Added the tag ‘gene-therapy-trial’ as this gene is within the Gene Therapy Panel available here: https://panelapp.genomicsengland.co.uk/panels/412
Created: 14 May 2018, 9:57 a.m.

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): SPINK5 .PanelApp HGNC gene symbol check: SPINK5 . IUIS Disease: Comel-Netherton syndrome . IUIS Inheritance: AR .T cells: Decreased or normal, .B cells: Low Switched and non-switched B cells , .IUIS Other affected cells: N/A. IUIS Associated features: Congenital ichthyosis, bamboo hair, atopic diathesis, increased bacterial infections, failure to thrive. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Hyper IgE Syndromes (HIES)
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, 2:58 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: SPINK5, PanelApp HGNC gene symbol check: SPINK5, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Netherton syndrome / Netherton syndrome
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: SPINK5, GRID_Gene_Symbol: SPINK5, GRID_Transcript_ENS_Community submitted: ENST00000359874, GRID_Transcript_RefSeq: NM_006846.3, GRID_Transcript_ENS_used_on_Production: ENST00000359874
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Netherton syndrome 256500
  • Congenital ichthyosis, bamboo hair, atopic diathesis, increased bacterial infections, failure to thrive
  • Combined immunodeficiencies with associated or syndromic features
Tags
early-onset gene-therapy-trial
OMIM
605010
Clinvar variants
Variants in SPINK5
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 SPINK5.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to SPINK5.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to SPINK5.

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 SPINK5 were set to Netherton syndrome 256500, Congenital ichthyosis, bamboo hair, atopic diathesis, increased bacterial infections, failure to thrive, 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 SPINK5. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to SPINK5. Panel: Primary immunodeficiency disorders

13 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: spink5 has been classified as Green List (High Evidence).

13 Jun 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SPINK5 were set to 19683336; 10835624; 28832989; 28943498; 28289593

16 May 2018, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for SPINK5 were set to Netherton syndrome 256500

16 May 2018, Gel status: 3

Gene classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

19 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).

19 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).

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to SPINK5. Panel: Primary immunodeficiency disorders Phenotypes for gene SPINK5 were set to Netherton syndrome

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene SPINK5 were set to Netherton syndrome

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

SPINK5 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

SPINK5 was created by Louise Daugherty