A joint team consisting of researchers from Korea University’s College of Medicine (KUCM) and the Institute of Basic Science (IBS) confirmed that a single sequence mutation in the CYFIP2 gene could cause West syndrome, a rare brain development disease.

West syndrome occurs in less than six babies per 10,000 newborns, and it is an intractable disease with symptoms such as infantile spasm and epilepsy before the age of one with intellectual and developmental disorders afterwards.

The research team, led by Professor Han Ki-hoon of KUCM, observed that a number of CYFIP2 gene mutations were recently reported in genetic analysis of West syndrome patients conducted in foreign countries. Accordingly, they produced and analyzed mouse models for the hotspot mutation, p.Arg87Cys.

A hotspot mutation is a variant or mutation that occurs most frequently than other variants.

Consequently, the results demonstrated that the CYFIP2 genetically modified mice reproduced representative symptoms seen in patients with west syndrome, such as spasms, microencephaly, and developmental disorders, at an early age. Additionally, the researchers found that nerve cells were lost in the hippocampal region of the brain and hypergrowth of astrocytes and microglia as age progressed.

Also, the team found that the p.Arg87Cys mutation promotes CYFIP2 protein ubiquitination --a protein degradation process -- inhibiting the protein’s stability.

Professor Han said, "Through this study, we verified the causal relationship between the CYFIP2 gene mutation found in patients and the onset of West syndrome, and specifically identified the effect of the mutation on the CYFIP2 protein.”

The study entitled, "The CYFIP2 p.Arg87Cys neurologic defects and gradation of CYFIP2,” was published in the international journal, Annals of Neurology.