Clinical Variability Associated with the Recurrent Pathogenic Gain-of-function Variant, c.1370C>T in the HK1 Gene and Related Neurodevelopmental Disorder

Hexokinase 1 (HK1), encoded by the HK1 gene, catalyses the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate, the initial step of glycolysis. Pathogenic monoallelic gain-of-function variants in HK1 have been implicated in neurodevelopmental disorders with visual defects and brain anomalies (NEDVIBA). This report describes the first molecularly confirmed case from India of an individual harboring the recurrent de novo variant, c.1370C>T p. (Thr457Met) in HK1 in a heterozygous state. Furthermore, we provide a comprehensive review of previously reported patients and an analysis of the variable clinical phenotypes.