Compound heterozygous mutations of NTNG2 cause intellectual disability via inhibition of the CaMKII signaling

Netrin-G2 is a membrane-anchored protein known to play critical roles in neuronal circuit development and synaptic organization. In this study, we identify compound heterozygous mutations of c.547delC, p.(Arg183Alafs∗186) and c.605G > A, p.(Trp202X) in NTNG2 causing a syndrome exhibiting developmental delay, intellectual disability, hypotonia, and facial dysmorphism. To elucidate the underlying cellular and molecular mechanisms, CRISPR-Cas9 technology is employed to generate a knock-in mouse model expressing the R183Afs and W202X mutations. We report that the Ntng2