دورية أكاديمية
Neither a Novel Tau Proteinopathy nor an Expansion of a Phenotype: Reappraising Clinicopathology-Based Nosology
| العنوان: | Neither a Novel Tau Proteinopathy nor an Expansion of a Phenotype: Reappraising Clinicopathology-Based Nosology |
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| المؤلفون: | Luca Marsili, Jennifer Sharma, Alberto J. Espay, Alice Migazzi, Elhusseini Abdelghany, Emily J. Hill, Kevin R. Duque, Matthew C. Hagen, Christopher D. Stephen, Gabor G. Kovacs, Anthony E. Lang, Marios Hadjivassiliou, Manuela Basso, Marcelo A. Kauffman, Andrea Sturchio |
| المصدر: | International Journal of Molecular Sciences, Vol 22, Iss 14, p 7292 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | cerebellar ataxia, neurogenetics, movement disorders, postmortem, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The gold standard for classification of neurodegenerative diseases is postmortem histopathology; however, the diagnostic odyssey of this case challenges such a clinicopathologic model. We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia–ataxia syndrome with supranuclear gaze palsy, suspected to represent Niemann–Pick disease Type C. Postmortem evaluation unexpectedly demonstrated neurodegeneration with 4-repeat tau deposition in a distribution diagnostic of progressive supranuclear palsy (PSP). Whole-exome sequencing revealed a new heterozygous variant in TGM6, associated with spinocerebellar ataxia type 35 (SCA35). This novel TGM6 variant reduced transglutaminase activity in vitro, suggesting it was pathogenic. This case could be interpreted as expanding: (1) the PSP phenotype to include a spinocerebellar variant; (2) SCA35 as a tau proteinopathy; or (3) TGM6 as a novel genetic variant underlying a SCA35 phenotype with PSP pathology. None of these interpretations seem adequate. We instead hypothesize that impairment in the crosslinking of tau by the TGM6-encoded transglutaminase enzyme may compromise tau functionally and structurally, leading to its aggregation in a pattern currently classified as PSP. The lessons from this case study encourage a reassessment of our clinicopathology-based nosology. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 22147292 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/22/14/7292; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms22147292 |
| URL الوصول: | https://doaj.org/article/7ae52b70500343c29f13e64ded63079a |
| رقم الأكسشن: | edsdoj.7ae52b70500343c29f13e64ded63079a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22147292 14220067 16616596 |
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| DOI: | 10.3390/ijms22147292 |