ArticleAmerican journal of human genetics2019
Recessive Rare Variants in Deoxyhypusine Synthase, an Enzyme Involved in the Synthesis of Hypusine, Are Associated with a Neurodevelopmental Disorder.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- ODC1-associated astrocytic urea cycle dysregulation in age-related memory impairment.Biogerontology · 2026Article
- A gene therapy strategy for Deoxyhypusine Synthase (DHPS) syndrome.Research square · 2026Article
- Genetic and Phenotypic Features of the Five Known Polyaminopathies: A Critical Narrative Review.American journal of medical genetics. Part A · 2026Review
- Epithelial hypusination regulates Helicobacter pylori-induced gastric inflammation.Amino acids · 2026Article
- Crystallographic fragment screening supports tool compound discovery and reveals conformational flexibility in human deoxyhypusine synthase.Communications chemistry · 2026Article
- Genetic analysis of three familial cases of pure terminal 19p13.3 duplication caused by maternal balanced translocation t(19;21) (p13.3;p12).Frontiers in genetics · 2026Article
- Polyamine Metabolism in Brain Health and Disease.Neuropharmacology and therapy · 2026Article
- Case Report: A new patient expanding the clinical spectrum ofFrontiers in pediatrics · 2026Article
- Epithelial Hypusination Regulates Helicobacter pylori-induced Gastric Inflammation.Research square · 2025Article
- Identifying Immune Response Protein Biomarkers in Parkinson's-Related Cognitive Impairment and Depression.Molecular neurobiology · 2025Article
- eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy.Journal of neurodevelopmental disorders · 2025Review
- AlphaFold models of host-pathogen interactions elucidate the prevalence and structural modes of molecular mimicry.bioRxiv : the preprint server for biology · 2025Article
- Hypusinated and unhypusinated isoforms of the translation factor eIF5A exert distinct effects in models of pancreas development and function.The Journal of biological chemistry · 2025Article
- Collection, preparation, and biobanking of clinical specimens for analysis in polyaminopathies.Methods in enzymology · 2025Article
- ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity.Cell reports · 2024Article
- Deoxyhypusine synthase deficiency syndrome zebrafish model: aberrant morphology, epileptiform activity, and reduced arborization of inhibitory interneurons.Molecular brain · 2024Article
- The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.International journal of molecular sciences · 2024Review
- Homozygous missense variants in YKT6 result in loss of function and are associated with developmental delay, with or without severe infantile liver disease and risk for hepatocellular carcinoma.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Structural Insights into the Mechanisms Underlying Polyaminopathies.International journal of molecular sciences · 2024Review
- Bachmann-Bupp syndrome and treatment.Developmental medicine and child neurology · 2024Review
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 2 countries.
Funding
Abstract
Hypusine is formed post-translationally from lysine and is found in a single cellular protein, eukaryotic translation initiation factor-5A (eIF5A), and its homolog eIF5A2. Biosynthesis of hypusine is a two-step reaction involving the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). eIF5A is highly conserved throughout eukaryotic evolution and plays a role in mRNA translation, cellular proliferation, cellular differentiation, and inflammation. DHPS is also highly conserved and is essential for life, as Dhps-null mice are embryonic lethal. Using exome sequencing, we identified rare biallelic, recurrent, predicted likely pathogenic variants in DHPS segregating with disease in five affected individuals from four unrelated families. These individuals have similar neurodevelopmental features that include global developmental delay and seizures. Two of four affected females have short stature. All five affected individuals share a recurrent missense variant (c.518A>G [p.Asn173Ser]) in trans with a likely gene disrupting variant (c.1014+1G>A, c.912_917delTTACAT [p.Tyr305_Ile306del], or c.1A>G [p.Met1?]). cDNA studies demonstrated that the c.1014+1G>A variant causes aberrant splicing. Recombinant DHPS enzyme harboring either the p.Asn173Ser or p.Tyr305_Ile306del variant showed reduced (20%) or absent in vitro activity, respectively. We co-transfected constructs overexpressing HA-tagged DHPS (wild-type or mutant) and GFP-tagged eIF5A into HEK293T cells to determine the effect of these variants on hypusine biosynthesis and observed that the p.Tyr305_Ile306del and p.Asn173Ser variants resulted in reduced hypusination of eIF5A compared to wild-type DHPS enzyme. Our data suggest that rare biallelic variants in DHPS result in reduced enzyme activity that limits the hypusination of eIF5A and are associated with a neurodevelopmental disorder.
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