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: | Emily J. Hill, Andrea Sturchio, Matthew C. Hagen, Jennifer S. Sharma, Manuela Basso, Marios Hadjivassiliou, Anthony E. Lang, Kevin R Duque, Luca Marsili, Marcelo Andrés Kauffman, Alberto J. Espay, Alice Migazzi, Christopher D. Stephen, Gabor G. Kovacs, Elhusseini Abdelghany |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 7292, p 7292 (2021) |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Nosology, Pathology, Case Report, Cerebellar ataxia, Movement disorders, Neurogenetics, Postmortem, Female, Humans, Middle Aged, Neurodegenerative Diseases, Phenotype, Spinocerebellar Ataxias, Supranuclear Palsy, Progressive, Transglutaminases, tau Proteins, 0302 clinical medicine, Supranuclear Palsy, Biology (General), Spectroscopy, Neurodegeneration, General Medicine, Computer Science Applications, Chemistry, Spinocerebellar ataxia, medicine.symptom, medicine.medical_specialty, QH301-705.5, Catalysis, Progressive supranuclear palsy, Inorganic Chemistry, 03 medical and health sciences, Progressive, medicine, Physical and Theoretical Chemistry, neurogenetics, Molecular Biology, QD1-999, postmortem, business.industry, Organic Chemistry, medicine.disease, Supranuclear gaze palsy, eye diseases, 030104 developmental biology, movement disorders, cerebellar ataxia, business, 030217 neurology & neurosurgery |
| 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. |
| اللغة: | English |
| تدمد: | 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1261ed913153ac391d8c5144b03a7b14 http://europepmc.org/articles/PMC8329925 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1261ed913153ac391d8c5144b03a7b14 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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