KEIO RESEARCHERS INFORMATION SYSTEM

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2016.02

  University of Tsukuba, 人間総合科学研究科 疾患制御医学専攻

  Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士（医学）, University of Tsukuba, Dissertation, 2016.02

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Clinical characteristics of pulmonary non-tuberculous mycobacterial disease with CFTR variants in the Japanese population.

  Nagao G, Namkoong H, Tanaka H, Asakura T, Hara A, Fukunaga N, Kaji M, Azekawa S, Nakagawara K, Morita A, Kamata H, Nishimura T, Miya F, Kosaki K, Fukunaga K, Holland SM, Hasegawa N

  BMJ open respiratory research 13 ( 1 )  2026.02

  　View Summary

  Background Pulmonary non-tuberculous mycobacterial (NTM) disease is a respiratory infection with an increasing incidence worldwide, including Japan. Host factors may also be involved in the establishment of pulmonary NTM disease. Cystic fibrosis transmembrane conductance regulator (CFTR) variants are associated with pulmonary NTM disease and bronchiectasis. However, data on CFTR variants in the Japanese population remain limited. Objectives We aimed to determine the frequency of CFTR variants and the impact on the clinical features of pulmonary NTM disease and bronchiectasis in the Japanese population. Methods We analysed 458 patients with either pulmonary NTM disease, non-cystic fibrosis bronchiectasis or both at Keio University Hospital from February 2016 to March 2019. CFTR variants were identified using exome sequencing, Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). These variants were determined to be deleterious using CFTR2 and in silico tools. Clinical characteristics of patients with and without CFTR variants were compared in a 1:8 age-matched and sex-matched ratio. Additionally, exome sequencing was performed for the family of a patient with a family history of pulmonary NTM disease. Results Deleterious CFTR variants were identified in 16 patients (3.5%). One variant was identified by MLPA, and 15 by Sanger sequencing. All patients harboured a CFTR variant in one allele. Compared with matched controls, these patients had lower sputum culture conversion rates and higher rates of macrolide resistance. In one family cluster, members with pulmonary NTM disease were found to carry the same CFTR variant. Conclusions We defined the frequency and clinical characteristics of CFTR variants among the Japanese population with either pulmonary NTM disease, noncystic fibrosis bronchiectasis or both and found that patients with CFTR variants may be refractory to pulmonary Mycobacterium avium complex disease. Further comprehensive research is needed to assess the impact of CFTR variants on pulmonary NTM disease and bronchiectasis in non-European populations.

  • Access to Document (DOI)

• Recurrent Pneumothorax in PIEZO2-Related Arthrogryposis: Implications for the Mechanosensory Function of PIEZO2 in the Respiratory System.

  Nakato D, Ono I, Misu K, Miya F, Kosaki K

  Congenital anomalies 66 ( 1 ) e70045 2026.01

  ISSN  0914-3505

  • Access to Document (DOI)

• Augmenting cost-effectiveness in clinical diagnosis using extended whole-exome sequencing: SNVs, SVs, and beyond.

  Miya F, Nakato D, Suzuki H, Yamada M, Watanabe D, Takenouchi T, Kosaki K

  Journal of human genetics 71 ( 1 ) 13 - 21 2026.01

  ISSN  1434-5161

  　View Summary

  In standard short-read whole-exome sequencing (WES), capture probes are typically designed to target the protein-coding regions (CDS), and regions outside the exons—except for adjacent intronic sequences—are rarely sequenced. Although the majority of known pathogenic variants reside within the CDS as nonsynonymous variants, some disease-causing variants are located in regions that are difficult to detect by WES alone, such as deep intronic variants and structural variants, often requiring whole-genome sequencing (WGS) for detection. Moreover, WES has limitations in reliably identifying pathogenic variants within mitochondrial DNA or repetitive regions. Here, we propose a strategy to improve the diagnostic yield in a cost-effective manner by expanding the target design of WES beyond the CDS. As an illustrative example, we experimentally validated an extended WES approach covering intronic and untranslated regions (UTRs) of 188 genes listed in the Japanese public health insurance-covered multiple gene testing, intronic and UTRs of 81 genes listed in ACMG Secondary Findings (SF) v3.2, and 70 repeat regions associated with diseases. Additionally, the entire mitochondrial genome was targeted. We demonstrate the coverage of these extended regions based on experimental data and present case examples in which previously diagnosed pathogenic variants located outside the CDS were successfully detected using this approach. This strategy enables a substantial increase in the chance of achieving a definitive diagnosis for patients using WES alone, without requiring WGS, at a cost comparable to conventional WES. Our method has the potential to significantly shorten the diagnostic odyssey and represents a valuable approach in clinical genomics.

  • Access to Document (DOI)

• Reflex Sympathetic Dystrophy-Like unilateral Erythema Caused by a Germline SCN9A Variant

   2026

  • Access to Document (DOI)

• Refractory myoclonic epilepsy and progressive movement disorder arising from recurrent DHDDS variants in Japanese patients: a case series.

  Kobayashi Y, Sakuma S, Morimoto E, Fujii H, Yamada K, Hojo M, Miura M, Tohyama J, Miya F, Kato M, Saitsu H, Matsumoto N

  Brain & development 47 ( 6 ) 104478 2025.12

  ISSN  0387-7604

  　View Summary

  Objective: Heterozygous DHDDS variants have been associated with intellectual disability and seizures, with or without movement disorders. We aimed to expand the known phenotypic spectrum of DHDDS-related disorders by elucidating the clinical characteristics of Japanese patients with recurrent DHDDS variants. Methods: Patients with pathogenic DHDDS variants were recruited from individuals diagnosed with developmental and epileptic encephalopathy or progressive myoclonus epilepsies who were treated at the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital, or the Department of Pediatrics, Osaka Metropolitan University Graduate School of Medicine. DHDDS pathogenic variants were identified using exome sequencing. Medical records and neurophysiological data were retrospectively reviewed. Results: Three de novo recurrent pathogenic DHDDS variants were identified in four patients: c.632G>A, p.(Arg211Gln) in two; c.614G>A, p.(Arg205Gln) in one; and c.110G>A, p.(Arg37His) in one. Three patients with p.(Arg211Gln) or p.(Arg37His) presented with severe intellectual disability and intractable generalized epilepsy, characterized by myoclonic, myoclonic–atonic, and atonic seizures. Eyelid myoclonia was the initial manifestation in infancy. One patient with p.(Arg205Gln) had a relatively mild course, with focal epilepsy and less severe intellectual disability. Myoclonus and tremor were present from infancy in two patients with p.(Arg211Gln) or p.(Arg37His), and from childhood in the patient with p.(Arg205Gln). One patient with p.(Arg211Gln) exhibited polymicrogyria in the right frontal lobe. Among the three patients with generalized epilepsy, fenfluramine effectively reduced myoclonic seizures in one, while total corpus callosotomy markedly reduced myoclonic–atonic or atonic seizures with falls in another. Conclusion: DHDDS-related disorders should be considered in patients with intellectual disability, epilepsy with early-onset eyelid myoclonia and myoclonic or myoclonic–atonic seizures, and movement disorders, including myoclonus and tremor, with slow progression. We identified polymicrogyria as a novel finding in DHDDS patients. For drug-resistant epilepsy in these patients, corpus callosotomy and fenfluramine may represent promising treatment options, with this report providing specific insights into their efficacy.

  • Access to Document (DOI)

display all >>

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Q&A　読者質問箱　NGSを用いた遺伝学的検査の分析的妥当性の評価はどのように行っていますか?

  宮 冬樹

  検査と技術 ((株)医学書院)  53 ( 6 ) 625 - 627 2025.06

  ISSN  0301-2611

• 胎生疾患による死産を経験した家系に対する包括的ゲノム検査の有用性

  田中 雄也, 春日 義史, 山田 茉未子, 大谷 利光, 福武 麻里絵, 池ノ上 学, 鈴木 寿人, 宮 冬樹, 稲垣 昇, 小崎 健次郎, 田中 守

  日本周産期・新生児医学会雑誌 ((一社)日本周産期・新生児医学会)  61 ( Suppl.1 ) P188 - P188 2025.06

  ISSN  1348-964X

• 胎児に構造異常を認め人工妊娠中絶あるいは子宮内胎児死亡に至った家系に対する遺伝学的アプローチ

  田中 雄也, 山田 茉未子, 春日 義史, 大谷 利光, 池ノ上 学, 鈴木 寿人, 宮 冬樹, 稲垣 昇, 田中 守, 小崎 健次郎

  日本小児科学会雑誌 ((公社)日本小児科学会)  129 ( 2 ) 179 - 179 2025.02

  ISSN  0001-6543

• 遺伝子バリアントが判明した新生児けいれん13例の検討

  大滝 里美, 寺西 宏美, 颯佐 かおり, 田中 萌子, 堀田 奈緒美, 櫻井 隼人, 本島 由紀子, 筧 紘子, 本多 正和, 石井 敦士, 加藤 光広, 宮 冬樹, 國方 徹也, 松本 浩, 山内 秀雄

  日本小児科学会雑誌 ((公社)日本小児科学会)  129 ( 2 ) 176 - 176 2025.02

  ISSN  0001-6543

• 薬剤抵抗性で重篤な経過をたどったGNAO1遺伝子の新規突然変異による発達性てんかん性脳症の女児例

  小林 良行, 立石 裕一, 出雲 大幹, 江口 勇太, 宮 冬樹, 加藤 光広, 岡田 賢

  てんかん研究 ((一社)日本てんかん学会)  42 ( 2 ) 462 - 462 2024.09

  ISSN  0912-0890

display all >>

Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• Exploration of longevity-related factors using blood somatic mutation and genomic association analysis in centenarians

  2024.04

  -

  2027.03

  Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  　View Summary

  血液中ではクローン性造血（CHIP）と呼ばれる特定の遺伝子の体細胞変異が選択的に増殖しクローン化している場合がある。CHIP保有者はがんや心血管疾患のリスクが高いことが知られている。CHIPの保有率は年齢依存性に上昇し、70歳では10％を超える。
  我々は百寿者（100歳以上）の全ゲノムシーケンスを進める過程で、超長寿者（110歳以上）では年齢依存的な予想よりもCHIP保有率が低いことを見出した。
  本研究は、CHIPの発生抑制と極端な長寿との間に関係があるとの仮説に基づき、約530名の百寿者について、80歳までの日本人（約7800人）とCHIPやゲノムの比較解析を行い、長寿関連因子の同定を目指す。

• 深層学習モデルで解き明かす発達性てんかん性脳症と脳形成異常の遺伝素因と画像診断

  2024.04

  -

  2027.03

  Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

  　View Summary

  脳形成異常とてんかん性脳症で全エクソーム解析を行い、多数の原因遺伝子を明らかにしたが、全ゲノム解析でも約40%は原因が分からず、新たな発想による解析法の開発が必要である。人工知能(AI)の深層学習モデルによる解析が急速に進歩しており、希少疾患でありながら多数の検体と画像の集積がある優位性を生かして、AIによる遺伝子解析とMRI画像解析を連携させた解析を行う。モザイクもしくは反復配列の挿入が隠れた原因と仮説を立て、AIによる変異検出と検証、AI画像診断による原因遺伝子予測法の開発を行う。

• Combining Artificial Intelligence and RNA-Seq to elucidate new etiologies of genetic neurological disorders in childhood.

  2020.04

  -

  2024.03

  Grants-in-Aid for Scientific Research, Kato Mitsuhiro, Grant-in-Aid for Scientific Research (C), No Setting

  　View Summary

  Rare and intractable neurological diseases with childhood onset are highly heritable. However, even with whole genome sequencing, the causative gene identification rate is around 60%. New analysis methods need to be developed. Using SpliceAI, a splice site prediction algorithm based on artificial intelligence (AI) technology, we detected variants that had not been detected by conventional splice site prediction algorithms. An expression study of the variants using LCL showed aberrant transcripts suggesting splice abnormalities. Exome data of 488 samples from the probands and their families were analyzed using SpliceAI. Seven pathogenic splicing variants were identified. We confirmed the usefulness of AI in detecting new genetic etiologies.

• 脳オルガノイドを用いた巨脳症発症メカニズムの解明

  2020.04

  -

  2024.03

  日本学術振興会（科研費）, 基盤研究(B) , Research grant, Coinvestigator(s)

• 人工知能 (AI) とRNA-Seqの融合による遺伝性小児神経疾患の新たな病態解明

  2020.04

  -

  2023.03

  日本学術振興会（科研費）, 基盤研究(C) , Research grant, Coinvestigator(s)

display all >>