The Potential Effect of Nav1.8 in Autism Spectrum Disorder: Evidence from a Congenital Case with Compound Heterozygous SCN10A Mutations [post]

Björn Heinrichs, Baowen Liu, Jin Zhang, Jannis E Meents, Kim Le, Petra Hautvast, Xiwen Zhu, Ningbo Li, Yi Liu, Markus Rothermel, Barbara Namer, Xianwei Zhang (+2 others)
2020 unpublished
Apart from the most prominent symptoms in Autism spectrum disorder (ASD), namely deficits in social interaction and repetitive behavior, patients often show abnormal sensory reactivity to environmental stimuli. Especially potentially painful stimuli are reported to be experienced in a different way compared to healthy persons. In our present study, we present an ASD patient carrying compound heterozygous mutations in the voltage-gated sodium channel (VGSC) Nav1.8, which is preferentially
more » ... ed in sensory neurons. We expressed both identified mutations, p.I1511M and p.R512X, in a heterologous expression system and investigated their biophysical properties using patch-clamp recordings. The results of these experiments suggest that both mutations lead to different degrees of loss-of-function of Nav1.8. Behavioral experiments in a Nav1.8 loss-of-function mouse model additionally revealed Nav1.8 may play a role in autistic behavior. Our results present Nav1.8 as a protein potentially involved in ASD pathophysiology and may therefore offer new insights to the genetic basis of this disease.
doi:10.21203/rs.3.rs-86011/v1 fatcat:wd6thpvnuzdx3gbhy4gdmn5rqe