From genomic variants to bedside decisions: precision diagnostics for pediatric primary immunodeficiency and autoinflammatory syndromes

Next-generation sequencing has redefined the diagnostic journey for children with atypical immunodeficiency or autoinflammatory phenotypes. Yet, the transition from a genetic finding to a definitive diagnosis remains fraught with difficulty. The high frequency of variants of uncertain significance, alongside clinical presentations that defy traditional syndromic classification, creates a persistent gap between genomic discovery and clinical utility. This bottleneck hinders personalized medicine in pediatric immunology.This Research Topic seeks to unite clinical immunologists, geneticists, and functional biologists in a shared mission: closing the gap between genomic discovery and bedside decision-making in pediatric immunology. Our goal is to to move the field beyond mere variant calling toward functional resolution: how cellular and molecular assays can reclassify variants of uncertain significance, how novel biomarkers can shorten time-to-diagnosis, and how clinicians reason through cases where genetics and phenotype do not neatly align. By assembling mechanistic, translational, and case-based work in one collection, we hope to give clinicians and researchers practical frameworks for turning ambiguous genomic findings into actionable diagnoses.We welcome contributions addressing: functional validation: cellular and molecular assay for the resolution of variants of uncertain significance (VUS); translational biomarkers: novel cellular and molecular biomarkers that shorten time-to-diagnosis in suspected primary immunodeficiency or autoinflammatory disease; Integrative approaches: leveraging multi-omics and systems-immunology for better genotype-phenotype mapping; clinical decision science:: diagnostic algorithms and management pathways for atypical or non-syndromic presentations; clinical insight : case reports or case series illustrating complex diagnostic reasoning in the face of inclusive genetic findings. We invite Original Research, Reviews, Mini-Reviews, Case Reports, Methods, and Perspectives articles from clinical and basic-science groups alike. Topic editors: Fabien Touzot, Jacques G. Rivière, Belén Almejun Source: https://www.frontiersin.org/research-topics/86764/from-genomic-variants-to-bedside-decisions-precision-diagnostics-for-pediatric-primary-immunodeficiency-and-autoinflammatory-syndromes