Pathogenic mutations – disclosed by Next Generation Sequencing techniques - are heterogenous and include truncating, missense, splice-site, and deletion variants. No clear genotype-phenotype correlation. No statistically significant differences according to mutation type, even though mutations with loss-of-function effect (i.e. truncating, deletion, splicing variant) are most often associated to seizures than those deemed to be less deleterious for protein function (i.e. missense, in-frame deletion/duplication). CUL4B exerts direct effects on the brain's excitation-inhibition balance.
CUL4B