ArticleEuropean journal of human genetics : EJHG2020
DPH1 syndrome: two novel variants and structural and functional analyses of seven missense variants identified in syndromic patients.
Article in European journal of human genetics : EJHG, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Exploring the molecular basis of microphthalmia and anophthalmia: Insights from an Egyptian cohort.Molecular vision · 2026Article
- A pediatric case of diphthamide biosynthesis 1 gene defect presenting with developmental delay, short stature, dysmorphic features, and sparse hair (Loucks-Innes syndrome): a case report.Journal of medical case reports · 2025Article
- Fine-mapping genomic loci refines bipolar disorder risk genes.Nature neuroscience · 2025Article
- Recessive loss-of-function variants in DPH1 identified as the molecular cause in a sibling pair previously diagnosed with Fine-Lubinsky syndrome.American journal of medical genetics. Part A · 2025Article
- Functional Integrity of Radical SAM Enzyme Dph1•Dph2 Requires Non-Canonical Cofactor Motifs with Tandem Cysteines.Biomolecules · 2024Article
- EEF2-inactivating toxins engage the NLRP1 inflammasome and promote epithelial barrier disruption.The Journal of experimental medicine · 2023Article
- DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models.Disease models & mechanisms · 2023Article
- Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes.Molecular cell · 2023Article
- Translational fidelity and growth of Arabidopsis require stress-sensitive diphthamide biosynthesis.Nature communications · 2022Article
- A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2022Article
- The role of altered translation in intellectual disability and epilepsy.Progress in neurobiology · 2022Review
- Chromatin Accessibility of Human Mitral Valves and Functional Assessment of MVP Risk Loci.Circulation research · 2021Article
- De Novo variants in EEF2 cause a neurodevelopmental disorder with benign external hydrocephalus.Human molecular genetics · 2021Article
- Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy.European journal of human genetics : EJHG · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
DPH1 variants have been associated with an ultra-rare and severe neurodevelopmental disorder, mainly characterized by variable developmental delay, short stature, dysmorphic features, and sparse hair. We have identified four new patients (from two different families) carrying novel variants in DPH1, enriching the clinical delineation of the DPH1 syndrome. Using a diphtheria toxin ADP-ribosylation assay, we have analyzed the activity of seven identified variants and demonstrated compromised function for five of them [p.(Leu234Pro); p.(Ala411Argfs*91); p.(Leu164Pro); p.(Leu125Pro); and p.(Tyr112Cys)]. We have built a homology model of the human DPH1-DPH2 heterodimer and have performed molecular dynamics simulations to study the effect of these variants on the catalytic sites as well as on the interactions between subunits of the heterodimer. The results show correlation between loss of activity, reduced size of the opening to the catalytic site, and changes in the size of the catalytic site with clinical severity. This is the first report of functional tests of DPH1 variants associated with the DPH1 syndrome. We demonstrate that the in vitro assay for DPH1 protein activity, together with structural modeling, are useful tools for assessing the effect of the variants on DPH1 function and may be used for predicting patient outcomes and prognoses.
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