Whole-Exome Sequencing for Molecular Diagnosis of Paediatric Nephrotic Syndrome in Africa: A Call for Implementation

Abstract

Nephrotic syndrome (NS) is a common type of kidney disease in children, marked by protein loss in urine, swelling, and low blood protein levels. It is more severe and prevalent in children of African descent, particularly in steroid-resistant forms. Many cases are primary and linked to mutations in genes such as NPHS1, NPHS2, and WT1. While whole-exome sequencing (WES) has advanced the identification of genetic causes globally, its application in African settings remains limited, leaving many cases undiagnosed. This review explores the potential of WES in improving NS diagnosis among African paediatric populations. A literature search was conducted using PubMed, Scopus, and Medline for studies published between 2015 and 2025 focusing on the application of WES in paediatric NS among individuals of African descent. From the 12 articles retrieved, three met the inclusion criteria. These publications reported variants in NPHS1, NPHS2, WT1, PLCE1, COL4A3, COL4A5, TRPC6, and LAMB2 among South African and Egyptian cohorts. WES remains underutilised in African NS research, hindered by limited resources, cost, and underrepresentation in genomic databases. Nonetheless, preliminary evidence suggests WES may contribute to improving diagnosis and guiding treatment through the identification of population-specific pathogenic variants. Increased investment in genomic infrastructure is important for maximising potential benefits and improving diagnostic capabilities.