Upon identification of several isoforms of amyloid precursor protein (APP) mRNA with a deletion followed by an insertion that accounted for epigenetic control of genomic rearrangements of APP gene in fibroblasts of patients with LNS, Nguyen proposed a role of epistasis between mutated HPRT1 and APP genes affecting the regulation of alternative APP pre-mRNA splicing as a possible pathophysiological mechanism of the severe neurobehavioral phenotype of LNS (Nguyen, 2019). This evidence concerns the gene APP and Lesch-Nyhan syndrome.