Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SPINK5

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

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

Green List (high evidence)

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

• 19683336
• 10835624
• 28832989
• 28943498
• 28289593

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.

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.