Then, the research team identified two other male children with similar symptoms who also had ELF4 gene variants. This disorder is now termed “Deficiency in ELF4, X-linked,” or DEX for short. Now, an increasing number of cases are being identified.

Inflammatory diseases caused by a single gene mutation affect about 1 out of every 5,000 children.

“It is very exciting to start with patients who are sick and discover an unexpected new gene with a fundamental role in regulating inflammation.” said Carrie Lucas, an assistant professor of immunobiology at Yale School of Medicine.

According to the researchers, the symptoms experienced by the children in the study were similar to those associated with other inflammatory bowel diseases is thought to be caused by an overactive immune system response that damages tissues of the host

After identifying the ELF4 variant, they studied its effects in cultured cells from patients, as well as in mice using CRISPR gene-editing to introduce patient-derived ELF4 mutations.

They confirmed that the variant disrupted ELF4 function, and resulted in elevated inflammatory responses of a variety of immune cell types. The widespread effects of the variant suggest ELF4 and its target genes likely play a role in regulating inflammation in multiple diseases.

This gives us the opportunity to identify and study the effects not only of ELF4 but also the genes it regulates across immune cell types and inflammatory disease phenotypes. This will help us to create a new molecular roadmap relevant to understanding and treating human diseases.

Source: Medindia