DPH1 syndrome: two novel variants and structural and functional analyses of seven missense variants identified in syndromic patients
作者: Roser UrreiztiKlaus MayerGilad D. EvronyEdith SaidLaura Castilla-VallmanyaNeal A. L. CodyGuillem PlasenciaBruce D. GelbDaniel GrinbergUlrich BrinkmannBryn D. WebbSusanna Balcells
作者单位: 1Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, IBUB, IRSJD, CIBERER, Barcelona, Spain
2Roche Pharma Research and Early Development. Large Molecule Research, Roche Innovation Center, Munich, Nonnenwald 2, 82377, Penzberg, Germany
3Center for Human Genetics & Genomics, New York University Langone Health, New York, NY, USA
4Section of Medical Genetics, Mater dei Hospital, Msida, Malta
5Department of Anatomy and Cell Biology, University of Malta, Msida, Malta
6Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
7Sema4, Stamford, CT, USA
8Lead Molecular Design, S.L, Sant Cugat del Vallés, Spain
9Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
10Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
刊名: European Journal of Human Genetics, 2020, Vol.28 (1), pp.64-75
来源数据库: Springer Nature Journal
DOI: 10.1038/s41431-019-0374-9
英文摘要: Abstract(#br)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...
全文获取路径: Springer Nature  (合作)
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影响因子:4.319 (2012)

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