Advancing Trisomy 21 Diagnosis in Mali through Fluorescence In Situ Hybridization

Down syndrome, caused by an extra copy of chromosome 21, is the most common constitutional chromosomal disorder and a leading cause of intellectual disability worldwide. In low-resource settings such as Mali, limited access to cytogenetic testing often results in diagnoses based primarily on clinical features. The need to implement a rapid cytogenetic method such as fluorescence in situ hybridization (FISH) to diagnose trisomy 21 in Mali is imperative. We prospectively enrolled twelve individuals presenting clinical features of Down syndrome and carried out FISH on their samples using a chromosome 21–specific RUNX1 probe. In parallel, we performed conventional cytogenetic analysis using DAPI banding to assess chromosomal structural characterization. Interphase FISH analysis was successful in all 12 samples (100%) and consistently showed three RUNX1 signals per nucleus, confirming trisomy 21 in all patients, with no evidence of mosaicism above the assay detection threshold. Among the 11 cases with analyzable metaphases, combined DAPI banding and FISH identified nine cases of free trisomy 21 and two cases of Robertsonian translocation rob (21; 21). This study shows, for the first time in Mali, the successful use of FISH as a rapid and reliable diagnostic tool for trisomy 21. Its integration with conventional cytogenetics improves diagnostic precision, allows detection of structural rearrangements, and compensates for the limitations of metaphase-dependent analyses, providing a scalable model for genetic diagnostics in resource-limited settings.