Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome

Ichiro Yabe, Hiroaki Yaguchi, Yasutaka Kato, Yasuo Miki, Hidehisa Takahashi, Satoshi Tanikawa, Shinichi Shirai, Ikuko Takahashi, Mari Kimura, Yuka Hama, Masaaki Matsushima, Shinsuke Fujioka, Takahiro Kano, Masashi Watanabe, Shin Nakagawa, Yasuyuki Kunieda, Yoshio Ikeda, Masato Hasegawa, Hiroshi Nishihara, Toshihisa OhtsukaShinya Tanaka, Yoshio Tsuboi, Shigetsugu Hatakeyama, Koichi Wakabayashi, Hidenao Sasaki

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5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number819
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

ASJC Scopus subject areas

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    Yabe, I., Yaguchi, H., Kato, Y., Miki, Y., Takahashi, H., Tanikawa, S., Shirai, S., Takahashi, I., Kimura, M., Hama, Y., Matsushima, M., Fujioka, S., Kano, T., Watanabe, M., Nakagawa, S., Kunieda, Y., Ikeda, Y., Hasegawa, M., Nishihara, H., ... Sasaki, H. (2018). Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome. Scientific reports, 8(1), [819]. https://doi.org/10.1038/s41598-018-19198-0