Relevance to Autism

Mutations appear to give rise to Dravet Syndrome as well as distinct epilepsy-related disorders and also migraine. Missense mutations were observed in cases from multiple unrelated families, one of which presented with seizures and Asperger Syndrome (asymptomatic carriers were also seen in families, but missense variants were not observed in any of 304 controls (Osaka H et al.). Autism seems to be common amongst individuals with Dravet Syndrome but the report does not give a frequency for the 20 individuals studied (Wolff M et al.). Rare missense variants were observed in 4/299 AGRE families but none of 96 controls, and one of these variants was found previously in a child with juvenile myoclonic epilepsy (Weiss LA et al.). De novo variants in SCN1A, including multiple missense variants that were predicted to be damaging and one likely gene-disruptive variant, have been identified in ASD probands (O'Roak et al., 2011; O'Roak et al., 2012; O'Roak et al., 2012; De Rubeis et al., 2014; Yuen et al., 2017). Assessment of a cohort of 35 individuals with Dravet syndrome using standardized tools demonstrated that 11 patients (39%) had ASD according to the DSM5 classification and ADIR and ADOS2 (Ouss et al., 2018). Additional de novo missense variants in the SCN1A gene were identified in novel ASD probands from the Autism Sequencing Consortium in Satterstrom et al., 2020; subsequent TADA analysis in this report identified SCN1A as a candidate gene with a false discovery rate < 0.1.

Molecular Function

This gene encodes the large alpha subunit of the vertebrate voltage-gated sodium channel essential for the generation and propagation of action potentials, mainly in nerve and muscle.

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References

Model Summary

Scn1a plays critical roles in the spike output from PV interneurons and, furthermore, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures.

References