Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: PTEN

- PMID: 32588888 (2020) - Sequencing of the T-cell receptor variable-region β-chain using peripheral blood from patients with PTEN hamartoma tumour syndrome (PHTS), revealed that patients with PTEN variants had a skewed T- and B-cell gene repertoire, characterised by increased prevalence of high-frequency clones, compared to PTEN wild-type population.

Pten knock-in murine models similarly exhibited skewed immune repertoire compositions. Mutants also displayed B-cell hyperactivation and T-cell hyper-reactivity upon Toll-like-receptor stimulation. Decreases in nuclear but not cytoplasmic Pten levels were associated with reduced expression of the autoimmune regulator (Aire), indicating that nuclear PTEN likely regulates Aire expression via its emerging role in splicing regulation.

Authors speculate that such disruptions in central immune tolerance processes due to PTEN variants may impact individual stress responses and therefore predisposition to chronic inflammation, autoimmunity and cancer.

Created: 22 Sep 2020, 2:17 p.m. | Last Modified: 22 Sep 2020, 2:17 p.m.

Panel Version: 2.193

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• 32588888

I don't know

Agree amber rating

Created: 23 Oct 2019, 7:11 a.m. | Last Modified: 23 Oct 2019, 7:11 a.m.

Panel Version: 1.132

I don't know

agree with all the Amber genes

Created: 25 Sep 2019, 1:49 p.m. | Last Modified: 25 Sep 2019, 1:49 p.m.

Panel Version: 1.115

I don't know

The amber genes are covered on our targeted exome, we feel that these should be covered in the testing

Created: 25 Sep 2019, 1:44 p.m. | Last Modified: 25 Sep 2019, 1:44 p.m.

Panel Version: 1.114

I don't know

Cowden (macrocephaly, variable GDD, skin features, malignancy risk) - some patients reported to have primary immunodef / hypogammaglob. / lymphopaenia / T&B cell abn. / susceptibility to infections). Green association - relevant phenotype?

Created: 26 Sep 2019, 3:58 p.m. | Last Modified: 26 Sep 2019, 3:58 p.m.

Panel Version: 1.130

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 only enough evidence to rate this gene Amber.

Created: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.

Panel Version: 1.116

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 only enough evidence to rate this gene Amber

Created: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.

Panel Version: 1.116

Comment on list classification: Changed from Red to Amber. As discussed with the GMS Immunology Specialist Test Group webex call 28th March 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber- publication evidence supplied by expert

Created: 15 Aug 2019, 3:33 p.m. | Last Modified: 16 Aug 2019, 9:07 a.m.

Panel Version: 1.51

Comment on publications: publication added to support upgrading gene to Amber- suggested by Sophie Hambleton in the GMS Immunological Specialist Test Group webex call 28th March 2019

Created: 29 Mar 2019, 12:56 p.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): PTEN .PanelApp HGNC gene symbol check: PTEN . IUIS Disease: PTEN Deficiency . IUIS Inheritance: AD .T cells: Normal, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Lymphoproliferation, Autoimmunity. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in at Least 2 Serum Immunoglobulin Isotypes with Normal or Low Number of B Cells, CVID Phenotype

Created: 6 Jul 2018, 12:33 p.m.