The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.

Signal peptide peptidase (SPP) is an ER-resident aspartyl intramembrane protease cleaving proteins within type II-oriented transmembrane segments. Here, we identified the tail-anchored protein Three prime repair exonuclease 1 (TREX1) as a novel substrate of SPP. Based on its DNase activity, TREX1 removes cytosolic DNA acting as a negative regulator of the DNA-sensing cGAS/STING pathway.

Accuracy of Bead Based Epitope Assay Testing for Peanut Allergy Diagnosis: Real-World Pediatric Population Study.

Background: Peanut allergy accounts for 25% of food allergic children, but current testing has a poor positive predictive value (PPV) and low accuracy, with peanut allergy over-diagnoses estimated to be greater than 60% in clinical settings. New methods for peanut allergy diagnosis via Bead-Based Epitope Assay (BBEA) testing with Ara h 2.008 and Ara h 2.

Investigation of a pathogenic inversion in UNC13D and comprehensive analysis of chromosomal inversions across diverse datasets.

Inversions are known contributors to the pathogenesis of genetic diseases. Identifying inversions poses significant challenges, making it one of the most demanding structural variants (SVs) to detect and interpret. Recent advancements in sequencing technologies and the development of publicly available SV datasets have substantially enhanced our capability to explore inversions.

The ClinGen Severe Combined Immunodeficiency Disease Variant Curation Expert Panel: Specifications for classification of variants in , , , , , , and .

Purpose: This collaborative study, led by the Clinical Genome Resource Severe Combined Immunodeficiency Disease Variant Curation Expert Panel (ClinGen SCID-VCEP), implemented and adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for interpreting germline variants in genes with established relationships to SCID. The effort focused on the 7 most common SCID-related genes identified by SCID newborn screening in North America: , , , , , , and .

Methods: The SCID-VCEP conducted a rigorous review of variants that involved database analyses, literature review, and expert feedback to derive gene-specific modifications to the ACMG/AMP guidelines.

Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.

Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.

Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed.