Two consanguineous families presenting with neuromuscular disease and epileptic encephalopathy were found to carry damaging homozygous variants in the SCN10A gene in Kambouris et al., 2016; additional compound heterozygous missense variants in this gene were subsequently identified in individuals with epilepsy and autism spectrum disorder. A compound heterozygous missense variant in SCN10A was observed in all three ASD-affected siblings in a multiplex family in Dhaliwal et al., 2021. Heinrichs et al., 2021 identified an ASD proband with a compound heterozygous mutation in SCN10A; functional assessment of the SCN10A variants observed in this proband (p.Arg512Ter and p.Ile1511Met) demonstrated complete loss of channel function and enhanced slow channel inactivation, respectively. Furthermore, behavioral experiments in a Scn10a loss-of-function mouse model in Heinrichs et al., 2021 showed that mutant mice displayed increased self-grooming, reduced nest building, and altered social behavior.
Molecular Function
The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Biallelic SCN10A mutations in neuromuscular disease and epileptic encephalopathy