MIYA Fuyuki



School of Medicine, Center for Medical Genetics (Shinanomachi)


Associate Professor (Non-tenured)

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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

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


Papers 【 Display / hide

  • The novel and recurrent variants in exon 31 of CREBBP in Japanese patients with Menke-Hennekam syndrome.

    Nishi E, Takenouchi T, Miya F, Uehara T, Yanagi K, Hasegawa Y, Ueda K, Mizuno S, Kaname T, Kosaki K, Okamoto N

    American journal of medical genetics. Part A (American Journal of Medical Genetics, Part A)   2021.10

    ISSN  1552-4825

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    Menke–Hennekam syndrome-1 (MKHK1) is a congenital disorder caused by the heterozygous variants in exon 30 or 31 of CREBBP (CREB binding protein) gene mapped on 16p13.3. It is characterized by psychomotor delay, variable impairment of intellectual disability (ID), feeding difficulty, autistic behavior, hearing impairment, short stature, microcephaly, and facial dysmorphisms. The CREBBP loss-of-function variants cause Rubinstein–Taybi syndrome-1 (RSTS1). The function of CREBBP leading to MKHK1 has not been clarified so far, and the phenotype of MKHK1 significantly differs from that of RSTS1. We examined six patients with de novo pathogenic variants affecting the last exon of CREBBP, and they shared the clinical features of MKHK1. This study revealed that one frameshift and three nonsense variants of CREBBP cause MKHK1, and inferred that the nonsense variants of the last exon could further help in the elucidation of the etiology of MKHK1.

  • Landscape of prognostic signatures and immunogenomics of the AXL/GAS6 axis in renal cell carcinoma.

    Hakozaki K, Tanaka N, Takamatsu K, Takahashi R, Yasumizu Y, Mikami S, Shinojima T, Kakimi K, Kamatani T, Miya F, Tsunoda T, Aimono E, Nishihara H, Mizuno R, Oya M

    British journal of cancer (British Journal of Cancer)   2021.10

    ISSN  0007-0920

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    Background: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis. Methods: To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC. We further applied genome-wide mutation analyses and methylation arrays. Results: Varying patterns of AXL and GAS6 expression were observed throughout primary RCC tumours and metastases. Scoring individual AXL/GAS6 levels in the tumour centre and invasive margin, namely, the AXL/GAS6 score, showed a good ability to predict the prognosis of clear cell RCC. Metastasis- and histological subtype-specific differences in the AXL/GAS6 score existed since lung metastasis and the papillary subtype were weakly related to the AXL/GAS6 axis. Cell-by-cell immunohistological assessments clarified an immunosuppressive environment in tumours with high AXL/GAS6 scores. Genomic alterations in the PI3K-mTOR pathway and DNA methylation profiling revealed distinct differences with the AXL/GAS6 score in ccRCC. Conclusion: The AXL/GAS6 scoring system could predict the outcome of prognosis and work as a robust biomarker for the immunogenomic state in RCC.

  • Four pedigrees with aminoacyl-tRNA synthetase abnormalities.

    Okamoto N, Miya F, Tsunoda T, Kanemura Y, Saitoh S, Kato M, Yanagi K, Kaname T, Kosaki K

    Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (Neurological Sciences)   2021.09

    ISSN  1590-1874

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    Aminoacyl tRNA synthetases (ARSs) are highly conserved enzymes that link amino acids to their cognate tRNAs. Thirty-seven ARSs are known and their deficiencies cause various genetic disorders. Variants in some ARSs are associated with the autosomal dominant inherited form of axonal neuropathy, including Charcot-Marie-Tooth (CMT) disease. Variants of genes encoding ARSs often cause disorders in an autosomal recessive fashion. The clinical features of cytosolic ARS deficiencies are more variable, including systemic features. Deficiencies of ARSs localized in the mitochondria are often associated with neurological disorders including Leigh and early-onset epileptic syndromes. Whole exome sequencing (WES) is an efficient way to identify the genes causing various symptoms in patients. We identified 4 pedigrees with novel compound heterozygous variants in ARS genes (WARS1, MARS1, AARS2, and PARS2) by WES. Some unique manifestations were noted. The number of patients with ARSs has been increasing since the application of WES. Our findings broaden the known genetic and clinical spectrum associated with ARS variants.

  • Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy.

    Takamatsu K, Tanaka N, Hakozaki K, Takahashi R, Teranishi Y, Murakami T, Kufukihara R, Niwa N, Mikami S, Shinojima T, Sasaki T, Sato Y, Kume H, Ogawa S, Kakimi K, Kamatani T, Miya F, Tsunoda T, Aimono E, Nishihara H, Sawada K, Imamura T, Mizuno R, Oya M

    Nature communications (Nature Communications)  12 ( 1 ) 5547 2021.09

     View Summary

    A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.

  • Two cases of DYNC1H1 mutations with intractable epilepsy.

    Matsumoto A, Kojima K, Miya F, Miyauchi A, Watanabe K, Iwamoto S, Kawai K, Kato M, Takahashi Y, Yamagata T

    Brain & development (Brain and Development)  43 ( 8 ) 857 - 862 2021.09

    ISSN  0387-7604

     View Summary

    Background: The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot–Marie–Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria. Case reports: Patient 1 had severe ID. At the age of 2 months, she presented myoclonic seizures and tonic seizures, and later experienced atonic seizures and focal impaired-awareness seizures (FIAS). EEG showed slow waves in right central areas during myoclonic seizures. Brain MRI revealed pachygyria, predominantly in the occipital lobe. After callosal transection her atonic seizures disappeared, but FIAS remained. Patient 2 was diagnosed with autism spectrum disorder (ASD) and severe ID. At the age of 7 years, he presented generalized tonic–clonic seizures, myoclonic seizures, and FIAS. Interictal EEG showed generalized spike-and-wave complexes, predominantly in the left frontal area. Brain MRI was unremarkable. Exome sequencing revealed novel de novo mutations in DYNC1H1: c.4691A > T, p.(Glu1564Val) in Patient 1 and c.12536 T > C, p.(Leu4179Ser) in Patient 2. Conclusions: DYNC1H1 comprises a stem, stalk, and six AAA domains. Patient 2 is the second report of an AAA6 domain mutation without malformations of cortical development. The p.(Gly4072Ser) mutation in the AAA6 domain was also reported in a patient with ASD. It may be that the AAA6 domain has little effect on neuronal movement of DYNC1H1 along microtubules.

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Reviews, Commentaries, etc. 【 Display / hide

  • KCNH1変異を有する小児例における新生児期からの脳波所見の経時的変化

    井上 武, 坂 京子, 谷村 知繁, 家田 大輔, 中村 勇治, 服部 文子, 齋藤 万里子, 宮 冬樹, 齋藤 伸治

    てんかん研究 ((一社)日本てんかん学会)  39 ( 2 ) 403 - 403 2021.07

    ISSN  0912-0890

  • 大頭と内反足を契機に診断したWest症候群を呈したCACNA1E変異を有する女児例

    草開 祥平, 平井 宏子, 田中 朋美, 藤木 靖子, 田中 千秋, 宮 一志, 本郷 和久, 宮 冬樹, 加藤 光広

    てんかん研究 ((一社)日本てんかん学会)  39 ( 2 ) 400 - 400 2021.07

    ISSN  0912-0890

  • 脳波所見から遺伝学的検査を考慮したSTXBP1遺伝子変異を有するWest症候群の男児例

    糸山 綾, 佐野 史和, 溝呂木 園子, 加賀 佳美, 金村 英秋, 宮 冬樹, 加藤 光広, 犬飼 岳史, 相原 正男

    てんかん研究 ((一社)日本てんかん学会)  39 ( 2 ) 402 - 402 2021.07

    ISSN  0912-0890

  • タンパク質立体構造解析を用いたインスリン/IGF-1受容体における遺伝子型-表現型相関の確立

    細江 隼, 鞁嶋 有紀, 宮 冬樹, 門脇 弘子, 鈴木 顕, 加藤 貴史, 岡田 随象, 角田 達彦, 花木 啓一, 神崎 晋, 庄嶋 伸浩, 山内 敏正, 門脇 孝

    糖尿病 ((一社)日本糖尿病学会)  64 ( Suppl.1 ) III - 105 2021.05

    ISSN  0021-437X

  • グアニジノ酢酸メチル基転移酵素欠損症に対するクレアチン・オルニチン補充の効果

    宮田 世羽, 井上 健司, 萩田 美和, 阿部 真麻, 大熊 こずえ, 福田 光成, 熊田 聡子, 宮 冬樹, 加藤 光広, 秋山 倫之, 楊 國昌

    脳と発達 ((一社)日本小児神経学会)  53 ( Suppl. ) S241 - S241 2021.05

    ISSN  0029-0831

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

  • 脳オルガノイドを用いた巨脳症発症メカニズムの解明


    日本学術振興会(科研費), 基盤研究(B) , Research grant, Co-investigator

  • 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


    日本学術振興会(科研費), 基盤研究(C) , Research grant, Co-investigator

  • 神経・筋相互作用を標的とした運動神経疾患の病態解明と治療開発


    日本医療研究開発機構(AMED),  疾患特異的iPS細胞の利活用促進・難病研究加速プログラム, Commissioned research, Co-investigator

  • 小児視覚聴覚二重障害の分子遺伝学的研究


    日本医療研究開発機構(AMED), 難治性疾患実用化研究事業, Commissioned research, Co-investigator

  • 網膜色素変性症に対する遺伝子特異的治療実現を目的とした、集約的遺伝解析とゲノム編集技術による病態解明


    日本医療研究開発機構(AMED), 難治性疾患実用化研究事業, Commissioned research, Co-investigator

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