CHOP Researchers Identify Novel Genetic Disorder Caused by MAP4K4 Gene Variants


There are still many unknowns when it comes to our genetics. How do gene variants of unknown significance (VUS) affect us? In what ways can we identify if variants are pathogenic (disease-causing)? Through exploring these questions—and many more—researchers are developing a deeper understanding of our genetic makeup. This includes identifying novel genetic conditions, such as a new genetic disorder caused by MAP4K4 variants. Previously, MAP4K4 has been implicated in the development of certain cancers, as well as a driver in neurodegenerative conditions. More information is needed to determine how these variants drive this novel genetic condition.

The Process of Uncovering a Rare and Novel Genetic Disorder

An article in Medical Xpress explains that a research team comprising members from Princeton University and the Children’s Hospital of Philadelphia identified this disorder after seeing several individuals presenting with craniofacial and neurodevelopmental concerns. The researchers believed that these individuals had an underlying genetic disorder—but weren’t exactly sure what it was. They asked people across the globe with specific symptoms and characteristics to reach out.

Altogether, the research team identified 36 patients from a total of 21 families globally. Further testing discovered potential gene variants within MAP4K4 that the researchers wanted to explore. The research team did so by creating zebrafish models of these rare variants. 

In their research, published in Science Advances, the research team genetically altered zebrafish embryos to have these variants. They found that the variants, which reduce MAP4K4 activity, interrupted RAS pathway signaling and caused developmental issues. 

Ultimately, more research is needed to better understand MAP4K4 gene variants, whether these variants are related to any other conditions, and how these affect overall health in those affected. Although this research may take time, gaining more knowledge on this rare genetic disorder can help other families find answers—and start the journey towards identifying potential therapies. 

Learn more about MAP4K4 and its link to cancer here.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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