The core challenge of modern preventive medicine is the accurate and timely identification of individuals at risk for genetic disorders. For decades, genetic testing has been gated by restrictive clinical criteria and "phenotype-first" models, which often rely on family history or specific symptoms to trigger a diagnostic workup. However, emerging evidence highlights a significant diagnostic gap: a substantial proportion of individuals carrying clinically actionable pathogenic variants are currently missed because they do not meet traditional testing guidelines or lack a documented family history of disease.

This Collection focuses on how the next generation of screening technologies can expand diagnostic capacity and maximize diagnostic yield. We are moving toward a "genome-first" era, in which criteria-independent testing and the integration of multimodal data enable the identification of individuals at risk who were previously undetected within the healthcare system. By leveraging advanced sequencing technologies and computational infrastructures, we can shift from reactive diagnostics to proactive, large-scale screening strategies that improve clinical outcomes across multiple medical disciplines.

Key Areas of Interest

We invite original research, reviews, and clinical perspectives that explore the technological and clinical pathways to increasing diagnostic sensitivity and specificity:

• Expanding the Diagnostic Net: Evaluating the clinical utility of criteria-independent or universal screening to identify high-risk individuals who would otherwise remain undetected under standard guidelines.
• Genome-First Implementation: Analysing the impact of population-based genomic screening in uncovering hereditary diseases or pathogenic variants associated with inherited diseases before the onset of clinical symptoms.
• Synergistic Diagnostic Modalities: The integration of DNA sequencing with other high-resolution markers, such as biochemical profiling or functional assays, to refine risk assessment and increase diagnostic precision.
• Opportunistic Screening and Secondary Findings: Best practices for managing and reporting actionable genetic findings discovered during routine clinical sequencing.
• Scalable Screening Architectures: Innovative approaches to integrating large-scale genetic data into healthcare systems, including the use of electronic health records to support automated risk identification.
• Overcoming Implementation Barriers: Strategies to mitigate disparities in access to screening, focusing on populations in which reliable family history information is limited.

All submissions in this Collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the Editor-in-Chief. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or the Editor-in-Chief.

This Collection showcases selected research presented at the 7th European GRIN Conference, where families, clinicians, and scientists gathered to explore the latest discoveries in GRI disorders.

The featured papers delve into the biology of NMDA and AMPA receptors, their gene variants, and their clinical implications, offering insights into complex symptomatology and emerging therapeutic approaches.

Reflecting the collaborative and translational nature of the event, this Collection bridges foundational science with real-world impact, aiming to improve outcomes for individuals affected by GRI-related conditions.

All submissions in this collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the Editor-in-Chief. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or the Editor-in-Chief.