DPYSL5encodes a member of the Dihydropyrimidinase-like (DPYSL) proteins, also designated as the Collapsin response mediators (CRMP) proteins, which constitute a family of five proteins abundantly expressed in the developing nervous system. The DPYSL proteins play major roles in variety of cellular process and DPYSL5 is a crucial regulator of neurite and dendrite growth dynamics during neuronal development.
Only missense variants were identified in all patients, including two recurrent variants: p.Glu41Lys and p.Glu25Lys. All individuals with these two recurrent variants display an agenesis of corpus callosum which is a neuroanatomical malformation already associated with ASD and ID.
Functional studies using neuronal cell cultures to model the impact of these variants on neural development have demonstrated impaired growth of neuronal projections.
DPYSL5