The cause of immune dysregulation in patients with PHTS is likely due to a combination of factors, including differential B-cell apoptosis, proliferation, and differentiation11; lymphopenia as a risk factor for autoimmunity37; potential abnormalities in the follicular T-cell compartment, as demonstrated in PTEN-deleted T cells in mice38; or alterations in Treg cells during inflammation or cellular stress. This evidence concerns the gene PTEN and lymphopenia.