Figure 8. Schematic and summary model of HPRT-deficiency role in dysregulating striatal gene expression and signaling.

HPRT-deficiency alters the purine pool; and via mechanisms that are still ill-defined, these alterations affect the gene expression of keys striatal-enriched transcription factors such as Ascl1, Bcl11b and Foxp1, notably during neurodevelopment. Later in mature neurons, these transcription factors control (directly or indirectly) the expression of several genes among them, Darpp-32 and Bdnf, whose the dysregulation affects striatal neurons signaling and neurotransmission, thus contributing to LNS neurological phenotype.