Heterozygous loss of function of / leads to increased activated Arf6 and severe neurocognitive seizure phenotype in females.

Clinical presentations of mutations in the gene on the X-chromosome initially implicated to cause non-syndromic intellectual disability (ID) in males have expanded to include early onset seizures in males as well as in females. The molecular pathogenesis is not well understood, nor the mechanisms driving disease expression in heterozygous females. Using a CRISPR/Cas9-edited KO mouse model, we confirm the loss of mRNA expression and lack of Iqsec2 protein within the brain of both founder and progeny mice.