Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder
| العنوان: | Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder |
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| المؤلفون: | Ellen van Beusekom, Andrea K. Petersen, Alireza Sedaghat, Amir Sherafat, Henry Houlden, Mohammad Yahya Vahidi Mehrjardi, Laila Selim, Nihal M. Al Menabawy, Stephanie Efthymiou, Ender Karaca, Mohammadreza Dehghani, Alper Gezdirici, Neda Mazaheri, Reza Azizi Malamiri, Vincenzo Salpietro, Valentina Stanley, Leslie Durham, Christopher A. Walsh, Caroline Dias, Lieke L.M. Schaeken, James R. Lupski, Reza Maroofian, Hamid Galehdari, Selina Banu, Jaya Punetha, Edward Yang, Davut Pehlivan, Zeynep Coban-Akdemir, Elena Seiradake, Jennifer E. Posey, Maryam Najafi, Gholamreza Shariati, Joseph G. Gleeson, Céline Zheng, Jamileh Rezazadeh Varaghchi, Hans van Bokhoven, Daniel L. Polla, Jennifer N. Partlow, Jennifer Keller-Ramey, Tadahiro Mitani, Abolfazl Rad, Valeria V. Orlova, Shalini N. Jhangiani |
| المصدر: | American Journal of Human Genetics American Journal of Human Genetics, 105, 5, pp. 1048-1056 American Journal of Human Genetics, 105, 1048-1056 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Neurite, Adolescent, In silico, Mutation, Missense, autism, NTNG2, Biology, GPI-Linked Proteins, Whole Exome Sequencing, 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Neurodevelopmental disorder, Protein structure, Report, Exome Sequencing, Netrin, Genetics, medicine, Missense mutation, Humans, Exome, Global developmental delay, Child, Preschool, developmental delay, intellectual disability, neurodevelopmental disorder, Child, Preschool, Female, Homozygote, Intellectual Disability, Netrins, Neurodevelopmental Disorders, Pedigree, Genetics (clinical), Exome sequencing, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], medicine.disease, 030104 developmental biology, Mutation, Missense, 030217 neurology & neurosurgery |
| الوصف: | NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein. Functional experiments, including in silico analysis of the protein structure, in vitro assessment of cell surface expression, and in vitro knockdown, revealed potential mechanisms of pathogenicity of the variants, including loss of protein function and decreased neurite outgrowth. Our data indicate that appropriate expression of NTNG2 plays an important role in neurotypical development. |
| وصف الملف: | application/pdf |
| تدمد: | 0002-9297 1537-6605 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b84f035a1329a6d86df6250a6489b3b9Test https://doi.org/10.1016/j.ajhg.2019.09.025Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b84f035a1329a6d86df6250a6489b3b9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029297 15376605 |
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