Other studies have engineered hiPSCs with specific mutations associated with rare cases of autism with variable penetrance. Griesi-Oliveira et al. 150 derived hiPSCs and consequently neurons from an individual with non-syndromic autism with a de novo balanced translocation disruption of TRPC6, a cation channel that plays a fundamental role in calcium homeostatsis. The group showed that these TRPC6 mutant hiPSC-derived neurons had shorter and less arborized neurites, reduced density of dendritic spines, significantly lower density of VGLUT1 puncta, and, predictably, impaired sodium and calcium currents. Promisingly, restoration of TRPC6 expression or treatment with IGF1 or hyperforin (a TRPC6-specific agonist) partially corrected these abnormal neuronal phenotypes. In contrast to the majority of hiPSC models, Wang et al. used CRISPR/Cas technology to engineer in hiPSCs a heterozygous loss of function mutation for CDH8, an ATP-dependent chromatin remodeler strongly associated with rare cases of autism. The mutation produced differential expression of thousands of genes enriched in GO functions such as β-catenin/Wnt signaling in mutated neurons, demonstrating the combined power of genome engineering and hiPSCs 151. This literature is still emerging, and it will
