Common Variable Immunodeficiency

Gene: PTEN

Green List (high evidence)

- 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, 9:57 p.m. | Last Modified: 22 Sep 2020, 9:57 p.m.

Panel Version: 0.94

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Skewed immune repertoire composition

Publications

• 32588888

Green List (high evidence)

At least 4 unrelated probands with PTEN loss of function variants have been reported with hypogammaglobulinemia, fulfilling the common variable immunodeficiency (CVID) disorders diagnostic criteria.
On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list

Created: 21 Jul 2020, 6:02 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Macrocephaly/autism syndrome MIM#605309; Cowden syndrome 1 MIM#158350

Publications

• 27531073
• 27426521