Figure 1

Figure 1 Zebrafish in vivo functional assays can rapidly provide precious information to clinicians regarding the pathogenicity of variants of uncertain significance (VUS).

(A) Schematic timeline of infant development highlighting the clinical/timeframe dilemma for detection and confirmation of SMN1-VUS pathogenicity for early-onset SMA (Type I/II), i.e., treatments need to be implemented before the first major clinical signs. Available treatments are expensive and potentially harmful if unnecessary, emphasizing the need for rapid and innovative VUS-testing approaches within a timeframe that aligns with disease progression. (B) Zebrafish functional/complementation assays can quickly provide valuable information on VUS-pathogenicity in less than 3 months, supporting clinicians in their decision process and in a clinically helpful timeframe. This rapid testing framework is applicable not only to spinal muscular atrophy (SMA) but also to a wide range of pediatric diseases, offering significant benefits in clinical practice.