Missense mutation of sodium channel gene SCN2A
causes Dravet syndrome.
The patient was found to harbor a heterozygous insertion-deletion NM_021007.2:c.2350_2365delinsTGTACTATCCAACAGATACT (NP_066287.2:p.(Thr784Cysfs*45)) in the SCN2A
gene, which was confirmed by Sanger sequencing [Figure 1].
After treatment of both scrapie-infected Syrian hamster brain and ScN2a
cell lines with guanidinehydrochloride, which allows epitope unmasking in native [PrP.sup.Sc], the abnormal protein was primarily described intracellularly , where it was found to accumulate in lysosomes.
Scientists also identified the deleterious mutations variants in four novel, nine known, and eight candidate autism risk genes, including CAPRIN1 and AFF2 (both linked to FMR1 involved in fragile X syndrome), VIP (involved in social-cognitive deficits), and other genes such as SCN2A
and KCNQ2 (also linked to epilepsy), NRXN1, and CHD7, which causes ASD-associated CHARGE syndrome.
Although mutation of the equivalent residue from Q to lysine (K) in epitope-tagged mouse PrP had no effect on [PrP.sup.Sc] formation in transfected chronically infected ScN2A
cells, the effects of the Q-to-E substitution were not assessed (36).
A gain-of-function mutation in the sodium channel gene SCN2A
results in seizures and behavioral abnormalities.
Animal studies were also conducted in which mice were inoculated with mouse ScN2a
cells treated with various antibodies.
Ng et al., "Case-control association study of polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A
, SCN3A, SCN1B, and SCN2B and epilepsy," Human Genetics, vol.