دورية أكاديمية
أعرض في EDS

Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.

التفاصيل البيبلوغرافية
العنوان: Clinical and Pathological Features of FTDP-17 with MAPT p.K298_H299insQ Mutation.
المؤلفون: Morino H; Department of Medical Genetics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.; Department of Molecular Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.; Department of Clinical Neuroscience & Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Kurashige T; Department of Neurology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan., Matsuda Y; Department of Molecular Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan., Ono M; Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan., Sahara N; Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan., Miyasaka T; Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.; Laboratory of Physiology & Anatomy, Nihon University School of Pharmacy, Funabashi, Japan., Soeda Y; Faculty of Science, Gakushuin University, Tokyo, Japan., Shimada H; Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan.; Department of Functional Neurology & Neurosurgery, Center for Integrated Human Brain Science, Brain Research Institute, Niigata University, Niigata, Japan., Yamazaki Y; Department of Clinical Neuroscience & Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Takahashi T; Department of Clinical Neuroscience & Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Izumi Y; Department of Clinical Neuroscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan., Ito H; Department of Neurology, Wakayama Medical University, Wakayama, Japan., Maruyama H; Department of Clinical Neuroscience & Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan., Higuchi M; Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan., Arihiro K; Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan., Suhara T; Department of Functional Brain Imaging, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan., Takashima A; Faculty of Science, Gakushuin University, Tokyo, Japan., Kawakami H; Department of Molecular Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
المصدر: Movement disorders clinical practice [Mov Disord Clin Pract] 2024 Jun; Vol. 11 (6), pp. 720-727. Date of Electronic Publication: 2024 Apr 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 101630279 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2330-1619 (Electronic) Linking ISSN: 23301619 NLM ISO Abbreviation: Mov Disord Clin Pract Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Hoboken, NJ : Wiley, [2014]-
مواضيع طبية MeSH: Frontotemporal Dementia*/genetics , Frontotemporal Dementia*/pathology , Frontotemporal Dementia*/metabolism , Frontotemporal Dementia*/diagnosis , Mutation* , tau Proteins*/genetics , tau Proteins*/metabolism, Aged ; Female ; Humans ; Male ; Middle Aged ; Brain/pathology ; Brain/metabolism ; Chromosomes, Human, Pair 17/genetics ; Parkinsonian Disorders/genetics ; Parkinsonian Disorders/pathology ; Parkinsonian Disorders/metabolism ; Pedigree ; Supranuclear Palsy, Progressive/genetics ; Supranuclear Palsy, Progressive/pathology
مستخلص: Background: MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia.
Objectives: To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease.
Methods: Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing. We conducted tau protein microtubule polymerization assay, heparin-induced tau aggregation, and western blotting with brain lysate from an autopsy case. We also evaluated abnormal tau aggregation by using anti-tau antibody and PM-PBB3.
Results: We identified a variant, c.896_897insACA, p.K298_H299insQ, in the MAPT gene of affected patients. Similar to previous reports, most patients presented with atypical parkinsonism. Biochemical analysis revealed that the mutant tau protein had a reduced ability to polymerize microtubules and formed abnormal fibrous aggregates. Pathological study revealed frontotemporal lobe atrophy, midbrain atrophy, depigmentation of the substantia nigra, and four-repeat tau-positive inclusions in the hippocampus, brainstem, and spinal cord neurons. The inclusion bodies also stained positively with PM-PBB3.
Conclusions: This study confirmed that the insACA mutation caused FTDP-17. The affected patients showed symptoms resembling Parkinson's disease initially and symptoms of progressive supranuclear palsy later. Despite the initial clinical diagnosis of frontotemporal dementia in the autopsy case, the spread of lesions could explain the process of progressive supranuclear palsy. The study of more cases in the future will help clarify the common pathogenesis of MAPT mutations or specific pathogeneses of each mutation.
(© 2024 International Parkinson and Movement Disorder Society.)
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معلومات مُعتمدة: Takeda Science Foundation; 15K15083 Japan Society for the Promotion of Science; KAKENHI 26242085 Japan Society for the Promotion of Science
فهرسة مساهمة: Keywords: MAPT; Parkinson's disease; frontotemporal dementia with parkinsonism linked to chromosome 17; progressive supranuclear palsy; tau protein
المشرفين على المادة: 0 (MAPT protein, human)
0 (tau Proteins)
تواريخ الأحداث: Date Created: 20240412 Date Completed: 20240603 Latest Revision: 20240816
رمز التحديث: 20240816
مُعرف محوري في PubMed: PMC11145108
DOI: 10.1002/mdc3.14042
PMID: 38605589
قاعدة البيانات: MEDLINE
الوصف
تدمد:2330-1619
DOI:10.1002/mdc3.14042