Faculty Mentor
Dr. Elaine Vanterpool
Files
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Description
The DGUOK is a nuclear gene that codes for the enzyme deoxyguanosine kinase, an essential protein in maintaining mitochondrial DNA and producing mitochondria. Mutagens in this gene can result in deoxyguanosine kinase deficiency, an inherited disorder that disrupts liver, muscle, and cerebral function. Manifesting from biallelic pathogenic variants, Mitochondrial DNA Depletion Syndrome ((MDDS) is a clinically heterogeneous group of autosomal recessive mitochondrial disorders that significantly reduce the number of mitochondrial DNA (mtDNA) in the affected cells. This results in stifled ATP synthesis, decreased energy reserves, and cellular dysfunction. As such, energy-dependent tissues such as the liver, heart, skeletal muscles, and brain are vulnerable to mtDNA depletion. The two presentations of MDDS are Multi-systemic disease, characterized by psychomotor delays, rotary nystagmus, hypotonia, and severe progressive liver dysfunction, and Isolated Hepatic Failure, characterized by Hepatomegaly, Cholestasis, and liver failure. These disorders can cause progressive neurological impairment as well as liver failure. This syndrome prominently appears in neonates and infants but also afflicts the adult population. Infants with this disorder typically have hypoglycemia and lactic acidosis. MDDS is associated with DGUOK, MPV17, POLG, and other gene variants. Moreover, liver and muscle tissue samples show reduced mtDNA copy numbers, an increased number of mitochondria with abnormal cristae, and a combined deficiency of the liver respiratory chain complexes I, III, and IV. To identify the disorder, patients are tested for DGUOK deficiency through genetic testing utilizing biochemical derangements such as conjugated hyperbilirubinemia. As a result of poor prognosis in patients with DGUOK deficiency, liver transplants are generally encouraged except for those who have sustained significant neurological deterioration and abnormalities. The purpose of my CODE Research Project is to analyze MDDS and its correlation to Glu165Val, Val121Leu, and His66Gln deoxyguanosine kinase (DGUOK) gene variants.
Publication Date
4-1-2025
City
Huntsville
Disciplines
Biology
Recommended Citation
Vanterpool, Elaine and Harris, Ethan, "An Analysis of DGUOK Variants Associated with Mitochondrial DNA Depletion Syndrome" (2025). Student Posters. 178.
https://ouscholars.oakwood.edu/student-posters/178