Loss of TNR causes a nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus
| العنوان: | Loss of TNR causes a nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus |
|---|---|
| المؤلفون: | Georg F. Hoffmann, Chong Ae Kim, David J. Amor, Monique Elmaleh-Bergès, Axel Neu, João Paulo Kitajima, Fernando Kok, Anne Claude Tabet, Lance H. Rodan, Tim M. Strom, Laurence Perrin, Henry Houlden, Michael C. Kruer, Maja Hempel, Matias Wagner, Mehran Beiraghi Toosi, Yue C. Si, Eva Pipiras, Jonathan Levy, Ehsan Ghayoor Karimiani, Tatjana Bierhals, Fabíola Paoli Monteiro, Hanka Venselaar, Reza Maroofian, Mohammad Doosti, Julia G. Salomao, Sheng Chih Jin, Sabine Jung-Klawitter, Thomas Opladen, Somayeh Bakhtiari, Saskia B. Wortmann, Monica S Cooper |
| المصدر: | Genetics in Medicine, 22, 1061-1068 Genet. Med. 22, 1061-1068 (2020) Genetics in Medicine, 22, 6, pp. 1061-1068 |
| بيانات النشر: | Springer Nature, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Central Nervous System, Opisthotonus, Homozygote, Tnr, Spastic Tetraparesis, Cerebral Palsy, Exome Sequencing, Developmental Disorder, Biology, medicine.disease, Extracellular Matrix, Developmental disorder, Neurodevelopmental disorder, Muscle Spasticity, Neurodevelopmental Disorders, medicine, Humans, Tenascin-R, Spastic tetraparesis, Missense mutation, Spasticity, medicine.symptom, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Neuroscience, Genetics (clinical), Exome sequencing |
| الوصف: | Contains fulltext : 220941.pdf (Publisher’s version ) (Closed access) PURPOSE: TNR, encoding Tenascin-R, is an extracellular matrix glycoprotein involved in neurite outgrowth and neural cell adhesion, proliferation and migration, axonal guidance, myelination, and synaptic plasticity. Tenascin-R is exclusively expressed in the central nervous system with highest expression after birth. The protein is crucial in the formation of perineuronal nets that ensheath interneurons. However, the role of Tenascin-R in human pathology is largely unknown. We aimed to establish TNR as a human disease gene and unravel the associated clinical spectrum. METHODS: Exome sequencing and an online matchmaking tool were used to identify patients with biallelic variants in TNR. RESULTS: We identified 13 individuals from 8 unrelated families with biallelic variants in TNR sharing a phenotype consisting of spastic para- or tetraparesis, axial muscular hypotonia, developmental delay, and transient opisthotonus. Four homozygous loss-of-function and four different missense variants were identified. CONCLUSION: We establish TNR as a disease gene for an autosomal recessive nonprogressive neurodevelopmental disorder with spasticity and transient opisthotonus and highlight the role of central nervous system extracellular matrix proteins in the pathogenicity of spastic disorders. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1530-0366 1098-3600 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b47343478697bea7b38019996b84eb41Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b47343478697bea7b38019996b84eb41 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15300366 10983600 |
|---|