A collaborative research project led in part by the Indiana Biosciences Research Institute (IBRI) has resulted in the first description of a new monogenic disease, named, “DHPS Deficiency.”
Our study identified the first human mutations in the deoxyhypusine synthase (DHPS) gene and described certain cellular effects that result from these mutations. My lab worked closely with Dr. Wendy Chung, Kennedy Family Professor of Pediatrics in Medicine at Columbia University Vagelos College of Physicians and Surgeons, and her lab, as well as a large group of collaborating physicians and scientists to realize this breakthrough.
From the moment the initial scientific observations were made, as a team we knew that the study needed to be completed as quickly as possible. We were collectively motivated to begin to provide answers to those individuals and families affected by the disease as well as to tell the scientific community about this landmark discovery.
The study, which began in mid-2017, identified five people, mostly children, from four unrelated families, who all developed similar if not identical symptoms of unknown cause until the identification of the common DHPS mutations. DHPS is an enzyme that is essential for the production of the unique amino acid, hypusine, which works in every cell of the body to help make proteins. The function of DHPS is essential for life. The mutations we identified in the patients cause a reduction in DHPS enzyme activity, which leads to clinical symptoms that include neurodevelopmental delay and seizures.
The study was published Jan. 17, 2019, in the American Journal of Human Genetics. The article is entitled, “Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder.”
Breakthrough will help find others affected
This work is significant not only because it is the first description of a new monogenic disease, but as a result of the study’s publication, researchers will be able to find other affected individuals and families from around the world. We can also now direct our research toward finding an effective treatment so that one day, testing for DHPS Deficiency can be included when infants are screened for genetic diseases.
