Investigating the Neurodevelopment of FOXG1 Haploinsufficiency Syndrome in Urine-Derived iPSCs

Background: FOXG1 syndrome is a rare neurodevelopmental disorder characterized by a rare ASD characterized by seizures, an unusually small head size (microcephaly), intellectual disability, stereotyped movements, and limited social interaction. It is caused by a mutation or deletion of a single copy of the FOXG1 gene on chromosome 14.

Objectives: In this study, we aim to elucidate the role of FOXG1 in neurodevelopment and characterize cellular phenotypes of the disorder by modeling FOXG1 syndrome using induced pluripotent stem cells (iPSCs).

Methods: We generated urine-derived iPSC lines from a female patient with a ~ 3 MB deletion containing the FOXG1 gene, a sex-matched family member control, and an artificially induced FOXG1 knockout (KO) cell line using CRISPR/Cas9, and an isogenic control.

Results: Our FOXG1 ^+/- models recapitulate expected reductions in FOXG1 compared to controls in neural progenitor cells (NPCs) and act as viable models for FOXG1 syndrome in vitro.

Conclusions: Our goal is that by modelling FOXG1 haploinsufficiency syndrome in human iPSCs, we may better understand how a loss of FOXG1 leads to such profound neurodevelopmental deficits