Language
English
Publication Date
1-1-2025
Journal
Genetics in Medicine Open
DOI
10.1016/j.gimo.2025.103425
PMID
40469904
PMCID
PMC12135434
PubMedCentral® Posted Date
3-20-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Purpose: Hexokinase 1 (HK1) encodes a ubiquitously expressed hexokinase, which is responsible for the first step of glycolysis, phosphorylation of glucose to glucose-6-phosphate. Both autosomal recessive and dominant variants in this gene have previously been shown to cause human disease, and presently, there are clinical data available for 27 individuals with the monoallelic neurodevelopmental disorder with visual defects and brain anomalies. Delineation of the entire phenotypic spectrum and genotype-phenotype relations will aid in management and counseling decisions.
Methods: We present molecular and clinical data on 22 additional individuals with heterozygous, mostly de novo, variants in HK1. We also reviewed data from the published literature.
Results: The clinical manifestations of neurodevelopmental disorder with visual defects and brain anomalies include varying degrees of intellectual disability/developmental delay, hypotonia, epileptic encephalopathy, visual deficits, a Leigh syndrome spectrum pattern on brain magnetic resonance imaging, and elevated lactate in blood and cerebrospinal fluid, suggesting mitochondrial dysfunction. Based on severity, individuals can be classified into mild, moderate, severe, or lethal forms. In terms of genotype-phenotype correlation, we find that all individuals carrying a missense variant at the threonine 457 residue have severe clinical features.
Conclusion: HK1 should be included in mitochondrial disorder gene sequencing panels.
Keywords
Hexokinase, HK1, Leigh syndrome spectrum, Mitochondrial disorder, NEDVIBA
Published Open-Access
yes
Recommended Citation
Ng, Bobby G; Eklund, Erik A; Rosenfeld, Jill A; et al., "Autosomal Dominant HK1-Related Neurodevelopmental Disorder With Visual Defects and Brain Anomalies (NEDVIBA): An Emerging Mitochondrial Disorder" (2025). Faculty and Staff Publications. 5040.
https://digitalcommons.library.tmc.edu/baylor_docs/5040
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