Frequency and characteristics of the TBK1 gene variants in Japanese patients with sporadic amyotrophic lateral sclerosis

Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS)

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease, and the etiology of sporadic ALS is generally unknown. The TANK-binding kinase 1 (TBK1) gene was identified as an ALS gene contributing to a predisposition toward ALS. To reveal the frequency and characteristics of variants of the TBK1 gene in sporadic ALS patients in Japan, we analyzed the TBK1 gene by exome sequencing in a large Japanese cohort of 713 sporadic ALS patients and 800 controls. We identified known or potentially toxic rare variants of TBK1 gene in 9 patients (1.26%) with sporadic ALS, including 4 novel missense variants (p.V23I, p.H322R, p.R358C, and p.T478I) and 3 loss-of-function variants (p.R357X, p.P378_I379del, and p.T419_G420del). The odds ratio between sporadic ALS patients and controls was 10.2 (p = 0.008, 95% confidence interval = 1.67–62.47). These findings support the contribution of TBK1 to the etiology of sporadic ALS in Japanese patients.

Original languageEnglish
Pages (from-to)158.e15-158.e19
JournalNeurobiology of Aging
Volume64
DOIs
Publication statusPublished - Apr 1 2018

Fingerprint

Phosphotransferases
Amyotrophic Lateral Sclerosis
Genes
Exome
Poisons
Amyotrophic lateral sclerosis 1
Japan
Odds Ratio
Confidence Intervals

Keywords

  • Amyotrophic lateral sclerosis
  • Japan
  • Sporadic
  • TBK1
  • Variant

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Frequency and characteristics of the TBK1 gene variants in Japanese patients with sporadic amyotrophic lateral sclerosis. / Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS).

In: Neurobiology of Aging, Vol. 64, 01.04.2018, p. 158.e15-158.e19.

Research output: Contribution to journalArticle

Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS). / Frequency and characteristics of the TBK1 gene variants in Japanese patients with sporadic amyotrophic lateral sclerosis. In: Neurobiology of Aging. 2018 ; Vol. 64. pp. 158.e15-158.e19.
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abstract = "Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease, and the etiology of sporadic ALS is generally unknown. The TANK-binding kinase 1 (TBK1) gene was identified as an ALS gene contributing to a predisposition toward ALS. To reveal the frequency and characteristics of variants of the TBK1 gene in sporadic ALS patients in Japan, we analyzed the TBK1 gene by exome sequencing in a large Japanese cohort of 713 sporadic ALS patients and 800 controls. We identified known or potentially toxic rare variants of TBK1 gene in 9 patients (1.26{\%}) with sporadic ALS, including 4 novel missense variants (p.V23I, p.H322R, p.R358C, and p.T478I) and 3 loss-of-function variants (p.R357X, p.P378_I379del, and p.T419_G420del). The odds ratio between sporadic ALS patients and controls was 10.2 (p = 0.008, 95{\%} confidence interval = 1.67–62.47). These findings support the contribution of TBK1 to the etiology of sporadic ALS in Japanese patients.",
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AU - Sone, Jun

AU - Nakatochi, Masahiro

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AU - Izumi, Yuishin

AU - Morita, Mitsuya

AU - Taniguchi, Akira

AU - Kano, Osamu

AU - Oda, Masaya

AU - Kuwabara, Satoshi

AU - Abe, Koji

AU - Aiba, Ikuko

AU - Okamoto, Koichi

AU - Mizoguchi, Kouichi

AU - Hasegawa, Kazuko

AU - Aoki, Masashi

AU - Hattori, Nobutaka

AU - Onodera, Osamu

AU - Naruse, Hiroya

AU - Mitsui, Jun

AU - Takahashi, Yuji

AU - Goto, Jun

AU - Ishiura, Hiroyuki

AU - Morishita, Shinichi

AU - Yoshimura, Jun

AU - Doi, Koichiro

AU - Tsuji, Shoji

AU - Nakashima, Kenji

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N2 - Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease, and the etiology of sporadic ALS is generally unknown. The TANK-binding kinase 1 (TBK1) gene was identified as an ALS gene contributing to a predisposition toward ALS. To reveal the frequency and characteristics of variants of the TBK1 gene in sporadic ALS patients in Japan, we analyzed the TBK1 gene by exome sequencing in a large Japanese cohort of 713 sporadic ALS patients and 800 controls. We identified known or potentially toxic rare variants of TBK1 gene in 9 patients (1.26%) with sporadic ALS, including 4 novel missense variants (p.V23I, p.H322R, p.R358C, and p.T478I) and 3 loss-of-function variants (p.R357X, p.P378_I379del, and p.T419_G420del). The odds ratio between sporadic ALS patients and controls was 10.2 (p = 0.008, 95% confidence interval = 1.67–62.47). These findings support the contribution of TBK1 to the etiology of sporadic ALS in Japanese patients.

AB - Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease, and the etiology of sporadic ALS is generally unknown. The TANK-binding kinase 1 (TBK1) gene was identified as an ALS gene contributing to a predisposition toward ALS. To reveal the frequency and characteristics of variants of the TBK1 gene in sporadic ALS patients in Japan, we analyzed the TBK1 gene by exome sequencing in a large Japanese cohort of 713 sporadic ALS patients and 800 controls. We identified known or potentially toxic rare variants of TBK1 gene in 9 patients (1.26%) with sporadic ALS, including 4 novel missense variants (p.V23I, p.H322R, p.R358C, and p.T478I) and 3 loss-of-function variants (p.R357X, p.P378_I379del, and p.T419_G420del). The odds ratio between sporadic ALS patients and controls was 10.2 (p = 0.008, 95% confidence interval = 1.67–62.47). These findings support the contribution of TBK1 to the etiology of sporadic ALS in Japanese patients.

KW - Amyotrophic lateral sclerosis

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KW - Variant

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