2019 Fiscal Year Annual Research Report
Comprehensive genomic analysis on perisylvian syndrome
Project/Area Number |
17K10080
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Research Institution | Yokohama City University |
Principal Investigator |
宮武 聡子 横浜市立大学, 附属病院, 講師 (50637890)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 全エクソーム解析 / 傍シルビウス裂症候群 / 多少脳回 |
Outline of Annual Research Achievements |
傍シルビウス裂症候群は大脳のシルビウス裂周辺の脳形成異常や機能異常を呈する難治性疾患である。本研究は日本人の本疾患コホートに対して次世代シーケンサーを駆使した包括的なゲノム解析を行い、本疾患の責任遺伝子の同定と病態解明を目的とする。 本年度はさらに19家系に対して全エクソーム解析を行った。遺伝子のコーディング領域を中心に、塩基置換、微小欠失や挿入配列変化、もしくはコピー数異常について、昨年度全エクソーム解析を行った103例と合わせ、症例で共通する病的な配列変化や構造異常の探索を継続している。 本年度は傍シルビウス裂症候群を引き起こすあらたな疾患責任遺伝子Xを確定し、論文投稿中である。本遺伝子は、機能性脳疾患の原因遺伝子として知られているが、従来大脳の形成異常は伴わないと考えられていたので、今回の発見は臨床的に非常に重要と考えられる。今回7症例の解析から、7つの病的変異を同定した。また結晶構造モデル解析やin vitroの機能解析から、すでに知られている機能性脳疾患の原因変異とは性質が異なることを明らかにした。モデル動物を用いて、今回同定した変異によって患者さんの表現型を裏付ける所見が確認され、その病態が示唆される結果を得た。 これまで3年間の研究で、2019年に論文発表したSCN3A、現在論文投稿中の遺伝子Xに加え、3つの新規遺伝子において、傍シルビウス裂症候群の疾患責任遺伝子と考えられる所見を見だしている。このうち1つの遺伝子については現在までに国内外の7症例を集積し、in vitroおよびin vivoの検証を進めている。また2つの遺伝子については、他施設共同研究を進めている。
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[Journal Article] Gain-of-Function MN1 Truncation Variants Cause a Recognizable Syndrome with Craniofacial and Brain Abnormalities2020
Author(s)
Miyake N, Takahashi H, Nakamura K, Isidor B, Hiraki Y, Koshimizu E, Shiina M, Sasaki K, Suzuki H, Abe R, Kimura Y, Akiyama T, Tomizawa SI, Hirose T, Hamanaka K, Miyatake S, Mitsuhashi S, Mizuguchi T, Takata A, Obo K, Kato M, Ogata K, Matsumoto N.
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Journal Title
Am J Hum Genet
Volume: 106
Pages: 13-25
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Phenotype-genotype correlations in patients with GNB1 gene variants, including the first three reported Japanese patients to exhibit spastic diplegia, dyskinetic quadriplegia, and infantile spasms2020
Author(s)
Endo W, Ikemoto S, Togashi N, Miyabayashi T, Nakajima E, Hamano SI, Shibuya M, Sato R, Takezawa Y, Okubo Y, Inui T, Kato M, Sengoku T, Ogata K, Hamanaka K, Mizuguchi T, Miyatake S, Nakashima M, Matsumoto N, Haginoya K.
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Journal Title
Brain Dev
Volume: 42
Pages: 199-204
DOI
Peer Reviewed
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[Journal Article] Long-read sequencing identifies the pathogenic nucleotide repeat expansion in RFC1 in a Japanese case of CANVAS2020
Author(s)
Nakamura H, Doi H, Mitsuhashi S, Miyatake S, Katoh K, Frith MC, Asano T, Kudo Y, Ikeda T, Kubota S, Kunii M, Kitazawa Y, Tada M, Okamoto M, Joki H, Takeuchi H, Matsumoto N, Tanaka F.
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Journal Title
J Hum Genet
Volume: 65
Pages: 475-480
DOI
Peer Reviewed
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[Journal Article] De Novo Truncating Variants in the Last Exon of SEMA6B Cause Progressive Myoclonic Epilepsy2020
Author(s)
Hamanaka K, Imagawa E, Koshimizu E, Miyatake S, Tohyama J, Yamagata T, Miyauchi A, Ekhilevitch N, Nakamura F, Kawashima T, Goshima Y, Mohamed AR, Ch'ng GS, Fujita A, Azuma Y, Yasuda K, Imamura S, Nakashima M, Saitsu H, Mitsuhashi S, Mizuguchi T, Takata A, Miyake N, Matsumoto N.
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Journal Title
Am J Hum Genet
Volume: 106
Pages: 549-558
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Genetic abnormalities in a large cohort of Coffin-Siris syndrome patients2019
Author(s)
Sekiguchi F, Tsurusaki Y, Okamoto N, Teik KW, Mizuno S, Suzumura H, Isidor B, Ong WP, Haniffa M, White SM, Matsuo M, Saito K, Phadke S, Kosho T, Yap P, Goyal M, Clarke LA, Sachdev R, McGillivray G, Leventer RJ, Patel C, Yamagata T, Osaka H, Hisaeda Y, Ohashi H, Miyatake S, Mizuguchi T, Miyake N, Matsumoto N, et al.
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Journal Title
J Hum Genet
Volume: 64
Pages: 1173-1186
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Comprehensive analysis of coding variants highlights genetic complexity in developmental and epileptic encephalopathy2019
Author(s)
Takata A, Nakashima M, Saitsu H, Mizuguchi T, Mitsuhashi S, Takahashi Y, Okamoto N, Osaka H, Nakamura K, Tohyama J, Haginoya K, Takeshita S, Kuki I, Okanishi T, Goto T, Sasaki M, Sakai Y, Miyake N, Miyatake S, Amamoto M, Takayama R, Hirabayashi S, Aiba K, Matsumoto H, Nabatame S, Shiihara T, Kato M, Matsumoto N, et al.
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Journal Title
Nature Communications
Volume: 10
Pages: 2506-2506
DOI
Peer Reviewed / Open Access
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[Journal Article] GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy2019
Author(s)
Okubo M, Doi H, Fukai R, Fujita A, Mitsuhashi S, Hashiguchi S, Kishida H, Ueda N, Morihara K, Ogasawara A, Kawamoto Y, Takahashi T, Takahashi K, Nakamura H, Kunii M, Tada M, Katsumoto A, Fukuda H, Mizuguchi T, Miyatake S, Miyake N, Suzuki J, Ito Y, Sone J, Sobue G, Takeuchi H, Matsumoto N, Tanaka F.
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Journal Title
Ann Neurol
Volume: 86
Pages: 962-968
DOI
Peer Reviewed
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[Journal Article] Comprehensive genetic analysis of 57 families with clinically suspected Cornelia de Lange syndrome2019
Author(s)
Aoi H, Mizuguchi T, Ceroni JR, Kim VEH, Furquim I, Honjo RS, Iwaki T, Suzuki T, Sekiguchi F, Uchiyama Y, Azuma Y, Hamanaka K, Koshimizu E, Miyatake S, Mitsuhashi S, Takata A, Miyake N, Takeda S, Itakura A, Bertola DR, Kim CA, Matsumoto N.
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Journal Title
J Hum Genet
Volume: 64
Pages: 967-978
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Mutations in PIGB Cause an Inherited GPI Biosynthesis Defect with an Axonal Neuropathy and Metabolic Abnormality in Severe Cases2019
Author(s)
Murakami Y, Nguyen TTM, Baratang N, Raju PK, Knaus A, Ellard S, Jones G, Lace B, Rousseau J, Ajeawung NF, Kamei A, Minase G, Akasaka M, Araya N, Koshimizu E, van den Ende J, Erger F, Rocha ME, Hashem MO, Aldhalaan HM, Alkuraya FS, Miyatake S, Matsumoto N, Krawitz PM, Rossignol E, Kinoshita T, Campeau PM, et al.
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Journal Title
Am J Hum Genet
Volume: 105
Pages: 384-394
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ataxic phenotype with altered CaV3.1 channel property in a mouse model for spinocerebellar ataxia 422019
Author(s)
Hashiguchi S, Doi H, Kunii M, Nakamura Y, Shimuta M, Suzuki E, Koyano S, Okubo M, Kishida H, Shiina M, Ogata K, Miyatake S, Miyake N, Saitsu H, Sato N, Ozaki K, Ohta K, Yokota T, Mizusawa H, Mitsui J, Ishiura H, Yoshimura J, Morishita S, Tsuji S, Takeuchi H, Ishikawa K, Matsumoto N, Ishikawa T, Tanaka F, et al.
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Journal Title
Neurobiology of Disease
Volume: 130
Pages: 104516~104516
DOI
Peer Reviewed
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[Journal Article] MYRF haploinsufficiency causes 46,XY and 46,XX disorders of sex development: bioinformatics consideration2019
Author(s)
Hamanaka K, Takata A, Uchiyama Y, Miyatake S, Miyake N, Mitsuhashi S, Iwama K, Fujita A, Imagawa E, Alkanaq AN, Koshimizu E, Azuma Y, Nakashima M, Mizuguchi T, Saitsu H, Wada Y, Minami S, Katoh-Fukui Y, Masunaga Y, Fukami M, Hasegawa T, Ogata T, Matsumoto N.
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Journal Title
Human Molecular Genetics
Volume: 28
Pages: 2319~2329
DOI
Peer Reviewed
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[Journal Article] Primary immunodeficiency with chronic enteropathy and developmental delay in a boy arising from a novel homozygous RIPK1 variant2019
Author(s)
Uchiyama Y, Kim CA, Pastorino AC, Ceroni J, Lima PP, de Barros Dorna M, Honjo RS, Bertola D, Hamanaka K, Fujita A, Mitsuhashi S, Miyatake S, Takata A, Miyake N, Mizuguchi T, Matsumoto N.
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Journal Title
J Hum Genet
Volume: 64
Pages: 955-960
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Hemorrhagic stroke and renovascular hypertension with Grange syndrome arising from a novel pathogenic variant in YY1AP12019
Author(s)
Saida K, Kim CA, Ceroni JRM, Bertola DR, Honjo RS, Mitsuhashi S, Takata A, Mizuguchi T, Miyatake S, Miyake N, Matsumoto N.
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Journal Title
J Hum Genet
Volume: 64
Pages: 885-890
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Single-fiber electromyography-based diagnosis of CACNA1A mutation in children: A potential role of the electrodiagnosis in the era of whole exome sequencing2019
Author(s)
Hirasawa-Inoue A, Ishiyama A, Takeshita E, Shimizu-Motohashi Y, Saito T, Komaki H, Nakagawa E, Yuasa S, Saitsu H, Hamanaka K, Miyatake S, Matsumoto N, Sasaki M.
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Journal Title
Brain Dev
Volume: 41
Pages: 905-909
DOI
Peer Reviewed
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[Presentation] Biallelic COLGALT1 variants as a novel genetic cause of cerebral small vessel disease2019
Author(s)
Satoko Miyatake,Norihisa Koyama, Kenji Yokochi, Kayo Ohmura, Eriko Koshimizu, Yuri Uchiyama, Hiroshi Doi, Hideyuki Takeuchi, Satomi Mitsuhashi, Mitsuko Nakashima, Takeshi Mizuguchi, Atsushi Takata, Noriko Miyake, Hirotomo Saitsu, Naomichi Matsumoto
Organizer
日本人類遺伝学会第64回大会
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