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Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome
Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770378/ https://www.ncbi.nlm.nih.gov/pubmed/29339765 http://dx.doi.org/10.1038/s41598-018-19198-0 |
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author | Yabe, Ichiro Yaguchi, Hiroaki Kato, Yasutaka Miki, Yasuo Takahashi, Hidehisa Tanikawa, Satoshi Shirai, Shinichi Takahashi, Ikuko Kimura, Mari Hama, Yuka Matsushima, Masaaki Fujioka, Shinsuke Kano, Takahiro Watanabe, Masashi Nakagawa, Shin Kunieda, Yasuyuki Ikeda, Yoshio Hasegawa, Masato Nishihara, Hiroshi Ohtsuka, Toshihisa Tanaka, Shinya Tsuboi, Yoshio Hatakeyama, Shigetsugu Wakabayashi, Koichi Sasaki, Hidenao |
author_facet | Yabe, Ichiro Yaguchi, Hiroaki Kato, Yasutaka Miki, Yasuo Takahashi, Hidehisa Tanikawa, Satoshi Shirai, Shinichi Takahashi, Ikuko Kimura, Mari Hama, Yuka Matsushima, Masaaki Fujioka, Shinsuke Kano, Takahiro Watanabe, Masashi Nakagawa, Shin Kunieda, Yasuyuki Ikeda, Yoshio Hasegawa, Masato Nishihara, Hiroshi Ohtsuka, Toshihisa Tanaka, Shinya Tsuboi, Yoshio Hatakeyama, Shigetsugu Wakabayashi, Koichi Sasaki, Hidenao |
author_sort | Yabe, Ichiro |
collection | PubMed |
description | Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer’s disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis. Whole-exome analysis of this family identified a novel missense mutation in BSN. Within the pedigree, the detected BSN mutation was found only in affected individuals. Further genetic analyses were conducted in probands from four other pedigrees with PSP-like syndrome and in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed in databases of healthy subjects were found in four sporadic cases. Western blot analysis of tau following the overexpression of wild-type or mutated BSN revealed the possibility that wild-type BSN reduced tau accumulation, while mutated BSN lost this function. An association between BSN and neurological diseases has not been previously reported. Our results revealed that the neurodegenerative disorder associated with the original proband’s pedigree is a novel tauopathy, differing from known dementia and parkinsonism syndromes, including PSP. |
format | Online Article Text |
id | pubmed-5770378 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57703782018-01-25 Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome Yabe, Ichiro Yaguchi, Hiroaki Kato, Yasutaka Miki, Yasuo Takahashi, Hidehisa Tanikawa, Satoshi Shirai, Shinichi Takahashi, Ikuko Kimura, Mari Hama, Yuka Matsushima, Masaaki Fujioka, Shinsuke Kano, Takahiro Watanabe, Masashi Nakagawa, Shin Kunieda, Yasuyuki Ikeda, Yoshio Hasegawa, Masato Nishihara, Hiroshi Ohtsuka, Toshihisa Tanaka, Shinya Tsuboi, Yoshio Hatakeyama, Shigetsugu Wakabayashi, Koichi Sasaki, Hidenao Sci Rep Article Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer’s disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis. Whole-exome analysis of this family identified a novel missense mutation in BSN. Within the pedigree, the detected BSN mutation was found only in affected individuals. Further genetic analyses were conducted in probands from four other pedigrees with PSP-like syndrome and in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed in databases of healthy subjects were found in four sporadic cases. Western blot analysis of tau following the overexpression of wild-type or mutated BSN revealed the possibility that wild-type BSN reduced tau accumulation, while mutated BSN lost this function. An association between BSN and neurological diseases has not been previously reported. Our results revealed that the neurodegenerative disorder associated with the original proband’s pedigree is a novel tauopathy, differing from known dementia and parkinsonism syndromes, including PSP. Nature Publishing Group UK 2018-01-16 /pmc/articles/PMC5770378/ /pubmed/29339765 http://dx.doi.org/10.1038/s41598-018-19198-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yabe, Ichiro Yaguchi, Hiroaki Kato, Yasutaka Miki, Yasuo Takahashi, Hidehisa Tanikawa, Satoshi Shirai, Shinichi Takahashi, Ikuko Kimura, Mari Hama, Yuka Matsushima, Masaaki Fujioka, Shinsuke Kano, Takahiro Watanabe, Masashi Nakagawa, Shin Kunieda, Yasuyuki Ikeda, Yoshio Hasegawa, Masato Nishihara, Hiroshi Ohtsuka, Toshihisa Tanaka, Shinya Tsuboi, Yoshio Hatakeyama, Shigetsugu Wakabayashi, Koichi Sasaki, Hidenao Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome |
title | Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome |
title_full | Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome |
title_fullStr | Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome |
title_full_unstemmed | Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome |
title_short | Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome |
title_sort | mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770378/ https://www.ncbi.nlm.nih.gov/pubmed/29339765 http://dx.doi.org/10.1038/s41598-018-19198-0 |
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