Targeted Next-Generation Sequencing for Improved Clinical Outcomes in People Living with Rare Diseases in Global South; A systematic review and Meta-synthesis Protocol (Preprint)

<sec> <title>BACKGROUND</title> Rare diseases affect many individuals and pose major challenges in diagnosis and treatment, especially in Global South countries where healthcare resources are limited. Targeted Next-Generation Sequencing (NGS) has significantly advanced diagnostic accuracy and clinical care for rare diseases globally, yet its implementation and impact within the Global South context remain insufficiently studied. </sec> <sec> <title>OBJECTIVE</title> Thus, this study aims to evaluate the use, clinical benefits, challenges, and implementation outcomes of Targeted NGS for diagnosing and managing rare diseases in Global South populations. </sec> <sec> <title>METHODS</title> This systematic review and meta-analysis protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will systematically search PubMed, Scopus, Web of Science, Embase, AJOL, and Google Scholar for studies published between 2005 and 2025 that report on the use of targeted NGS in Global South population with rare diseases. Two reviewers will independently perform study selection, data extraction, quality assessment, and evaluation of risk of bias, using the Risk of Bias Assessment Tool for non-randomised studies. Meta-analyses will be conducted to estimate pooled outcomes, with heterogeneity assessed using random-effects models. Heterogeneity will be further examined through visual inspection of forest plots and by evaluating the χ² test and I² statistic. </sec> <sec> <title>RESULTS</title> The protocol has obtained waiver from the ethics committee of Sefako Makgatho Health Sciences University (SMUREC/M/364/2025), as it does not involve the collection of original data. </sec> <sec> <title>CONCLUSIONS</title> The findings will be disseminated through peer-reviewed publications, conference presentations, and engagement with healthcare stakeholders in the Global South to inform policy and practice. </sec> <sec> <title>CLINICALTRIAL</title> PROSPERO registration number available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251078455 </sec>