Investigating the pathomechanisms of FOXG1 syndrome
- Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
- Transgenic Animal Unit, Mark Wainwright Analytical Centre, UNSW, Sydney, New South Wales, Australia.
FOXG1 syndrome is a neuro-developmental disorder that affects the early development of the telencephalon leading to severe cortical impairments. Patients typically present with post-natal microcephaly, severe mental retardation, apraxia and seizures. The disease is associated with mutations in the FOXG1 gene, which encodes a transcription factor belonging to the forkhead family. Here we report a novel mutation of the FOXG1 syndrome, a single nucleotide deletion c.946del (p.Leu316Cysfs*10) resulting in the premature truncation of the FOXG1 protein. We hypothesized that truncation of the FOXG1 protein leads to loss of potential interacting partners that may contribute to the pathology. To uncover these interacting partners, we performed immunoprecipitation of the FOXG1 protein and its mutant form in Neuro-2a cells. Subsequently, we performed mass spectrometry on purified extracts for identification. Our findings provide an insight into potential regulatory mechanisms of the physiological FOXG1 pathway and its pathological counterparts. Targeting the newly identified interaction partners could lead to new therapeutic strategies to abate the symptoms of the disease.