APPLICATIONS OF ALLELE-SPECIFIC PCR IN EARLY DETECTION OF HEREDITARY DISORDERS: A SYSTEMATIC REVIEW OF TECHNIQUES AND OUTCOMES

Abstract

This systematic review comprehensively investigates the diagnostic utility, methodological evolution, and translational impact of Allele-Specific Polymerase Chain Reaction (AS-PCR) in the detection and management of hereditary disorders. AS-PCR has established itself as a cornerstone in molecular diagnostics, primarily for its high specificity, affordability, operational simplicity, and rapid discrimination of single nucleotide polymorphisms (SNPs) and known point mutations. This review synthesizes findings from 86 peer-reviewed studies published between January 1990 and March 2023, encompassing diverse clinical and public health applications. The evidence reveals AS-PCR’s widespread use across monogenic disease diagnostics—including beta-thalassemia, cystic fibrosis, and Tay-Sachs disease—hereditary cancer syndromes such as BRCA1/2 and Lynch syndrome, prenatal and neonatal screening, and ethnically targeted carrier testing. The method consistently achieves diagnostic sensitivity and specificity exceeding 95%, affirming its reliability for early genetic risk identification. Particularly in founder populations and consanguinity-prone regions, AS-PCR has supported national screening programs, preimplantation genetic diagnosis, and cascade testing with measurable reductions in disease incidence. In low- and middle-income countries (LMICs), AS-PCR’s compatibility with minimal laboratory infrastructure, use in mobile diagnostic units, and successful adaptation to dried blood spot and saliva samples further underscore its global relevance. Field studies from South Asia, the Middle East, and sub-Saharan Africa confirm AS-PCR’s capacity to deliver accurate results in decentralized, resource-constrained settings where sequencing technologies are often inaccessible. Despite its limitations in identifying novel or rare variants, AS-PCR remains a technically robust and clinically actionable tool, particularly in targeted screening frameworks. Its integration into public health initiatives and clinical workflows has broadened access to molecular diagnostics and facilitated preventive genetic medicine on a global scale. This review concludes that AS-PCR continues to be indispensable in personalized medicine, population genomics, and health equity strategies, especially in bridging the diagnostic gap across diverse healthcare systems.