Molecular Diagnosis of Hemophilia in the Era of Advanced Genomic Technology: Current Status and Future in Africa

Abstract

Molecular characterization of pathogenic variants in the F8 and F9 genes is central to accurate diagnosis, carrier detection, inhibitor risk stratification, and emerging gene-based therapies in hemophilia A and B. Although next-generation sequencing (NGS)–based diagnostic algorithms now achieve near-complete variant detection in high-income settings, their implementation remains severely limited across Africa, where fewer than 10% of expected hemophilia cases are diagnosed. This narrative review critically evaluates the current molecular diagnostic landscape for hemophilia in Africa, integrating available genetic data with analyses of diagnostic methodologies, detection rates, and systemic constraints. We synthesised data from peer-reviewed studies reporting molecular characterisation of F8 and F9 in African patients and analysed how methodological constraints shape the observed mutation spectrum. Across fewer than ten African countries, fewer than 200 patients have undergone molecular characterization, revealing marked allelic heterogeneity and a disproportionately high burden of novel F8 and F9 variants. However, most studies rely on low-throughput PCR-based strategies, resulting in incomplete detection of structural variants, deep intronic mutations, and complex rearrangements. Beyond cataloguing variants, this review provides a comparative, method-centric analysis of diagnostic yield, highlights the structural underrepresentation of African-derived variants in public databases, and proposes a resource-stratified genomic diagnostic framework tailored to African health systems. We argue that equitable hemophilia care in Africa will require not only expanded access to NGS technologies but also coordinated data sharing, functional variant interpretation, and integration of molecular diagnosis into clinical decision-making pathways.