Splice site and mutations can cause mixed dominant negative/gain of function -associated immune dysregulation with cold urticaria (CU-PLAID).

Background: Phospholipase Cγ2 (PLCγ2) is an important signaling molecule that receives and transmits signals from various cell surface receptors in most hematopoietic lineages. Variants of cause PLCγ2-associated immune dysregulation (PLAID), a family of conditions that are classified by mutational effect. PLAID with cold urticaria (CU-PLAID) is caused by in-frame deletions of that are dominant negative at physiologic temperatures but become spontaneously active at sub-physiologic temperatures.

PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.

Background: Pathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dominant immune dysregulation (ID), PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammatory PLAID (APLAID). Since describing these conditions, many PLCG2 variants of uncertain significance have been identified by clinical sequencing of patients with diverse features of ID.

Objective: We sought to functionally classify PLCG2 variants and explore known and novel genotype-function-phenotype relationships.

Elevated DDX21 regulates c-Jun activity and rRNA processing in human breast cancers.

Introduction: The DDX21 RNA helicase has been shown to be a nucleolar and nuclear protein involved in ribosome RNA processing and AP-1 transcription. DDX21 is highly expressed in colon cancer, lymphomas, and some breast cancers, but little is known about how DDX21 might promote tumorigenesis.

Methods: Immunohistochemistry was performed on a breast cancer tissue array of 187 patients.

Amyloid-β42 alters apolipoprotein E solubility in brains of mice with five familial AD mutations.

Amyloid plaques composed of the 42 amino acid form of amyloid-β peptide (Aβ42) are a pathological hallmark of Alzheimer's disease (AD), but soluble and intraneuronal Aβ42 are the more proximal causes of synaptic dysfunction and neurotoxicity. Apolipoprotein E (apoE) modulates this disease process, as inheritance of the ɛ4 allele of the apoE gene is the primary genetic risk factor for AD. To address the solubility of Aβ42 and apoE, the 5xFAD-specific extraction profile for Aβ42 was optimized, a protein extraction protocol was optimized in the presence of minimal to extensive Aβ42 pathology.