2016 Fiscal Year Annual Research Report
The search for causative gene in Coffin-Siris syndrome
| Project/Area Number |
15K19660
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| Research Institution | Kanagawa Children's Medical Center (Clinical Research Institute) |
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Principal Investigator |
鶴崎 美徳 地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 主任研究員 (70392040)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | Coffin-Siris症候群 / 次世代シークエンス解析 |
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| Outline of Annual Research Achievements |
Coffin-Siris症候群 (Coffin-Siris Syndrome，CSS) は、1970年にCoffin医師とSiris医師により、知的障害、小頭、発育不全、特異的顔貌、第5指・趾爪の低形成を特徴とする症候群として初めて報告された。遺伝形式は、家族の中には全く罹患者がみられない孤発例が大多数を占めるが、家族例や同胞例も報告されていることから、常染色体優性遺伝、常染色体劣性遺伝、X連鎖性遺伝も想定される。我々は世界で初めて、エクソンキャプチャー法と次世代シークエンス技術を組み合わせた、全エクソーム解析（WES）により、クロマチン再構成因子の1種であるBAF複合体の構成サブユニットをコードする遺伝子群、SMARCB1、SMARCA4、ARID1A、ARID1B、およびSMARCE1の5種類の遺伝子のいずれかに変異を認めた。この5種類の遺伝子群を病因としない未解決の症例も存在していることから、新たな遺伝子の関与が示唆されていた。そこで、WESにより網羅的遺伝子変異の探索を行ったところ、2症例においてSOX11のde novo変異を同定した。
本研究では、引き続きCSS症例を集積し、次世代シークエンサーを用いた網羅的遺伝子変異の探索を行った。その結果、これまで解析した全症例を含めて、148症例中88症例（59.5％）で、SMARCA4（14症例、15.9％）、SMARCB1（10症例、11.4％）、SMARCE1（2症例、2.3％）、ARID1A（6症例、6.8％）、ARID1B（54症例、61.4％）、あるいはSOX11（2症例、2.3％）に変異を認めた。
責任遺伝子が明らかになることにより、早期に遺伝子診断を行うことが可能となり、また病態が解明されることにより、早い段階で適切な療育が施され、患児の長期的予後は改善することが期待される。
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[Journal Article] Biallelic Mutations in MYPN, Encoding Myopalladin, Are Associated with Childhood-Onset, Slowly Progressive Nemaline Myopathy2017
Author(s)
Miyatake S, Mitsuhashi S, Hayashi YK, Purevjav E, Nishikawa A, Koshimizu E, Suzuki M, Yatabe K, Tanaka Y, Ogata K, Kuru S, Shiina M, Tsurusaki Y, Nakashima M, Mizuguchi T, Miyake N, Saitsu H, Ogata K, Kawai M, Towbin J, Nonaka I, Nishino I, Matsumoto N.
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Journal Title
Am J Hum Genet.
Volume: 100 (1)
Pages: 169-178
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Somatic mutations in GLI3 and OFD1 involved in sonic hedgehog signaling cause hypothalamic hamartoma2016
Author(s)
Saitsu H, Sonoda M, Higashijima T, Shirozu H, Masuda H, Tohyama J, Kato M, Nakashima M, Tsurusaki Y, Mizuguchi T, Miyatake S, Miyake N, Kameyama S, Matsumoto N.
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Journal Title
Ann Clin Transl Neurol.
Volume: 3(5)
Pages: 356-365
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] De novo GABRA1 mutations in Ohtahara and West syndromes2016
Author(s)
Kodera H, Ohba C, Kato M, Maeda T, Araki K, Tajima D, Matsuo M, Hino-Fukuyo N, Kohashi K, Ishiyama A, Takeshita S, Motoi H, Kitamura T, Kikuchi A, Tsurusaki Y, Nakashima M, Miyake N, Sasaki M, Kure S, Haginoya K, Saitsu H, Matsumoto N.
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Journal Title
Epilepsia
Volume: 57(4)
Pages: 566-573
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] De novo KCNH1 mutations in four patients with syndromic developmental delay, hypotonia and seizures2016
Author(s)
Fukai R, Saitsu H, Tsurusaki Y, Sakai Y, Haginoya K, Takahashi K, Hubshman MW, Okamoto N, Nakashima M, Tanaka F, Miyake N, Matsumoto N.
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Journal Title
J Hum Genet.
Volume: 61(5)
Pages: 381-387
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Human genetic variation database, a reference database of genetic variations in the Japanese population2016
Author(s)
Higasa K, Miyake N, Yoshimura J, Okamura K, Niihori T, Saitsu H, Doi K, Shimizu M, Nakabayashi K, Aoki Y, Tsurusaki Y. et al.
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Journal Title
J Hum Genet.
Volume: 61(6)
Pages: 547-553
DOI
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases2016
Author(s)
Zarate YA, Bhoj E, Kaylor J, Li D, Tsurusaki Y, Miyake N, Matsumoto N, Phadke S, Escobar L, Irani A, Hakonarson H, Schrier Vergano SA.
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Journal Title
Am J Med Genet A.
Volume: 170 (8)
Pages: 1967-1973
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Different X-linked KDM5C Mutations in Affected Male Siblings: Is Maternal Reversion Error Involved?2016
Author(s)
Fujita A, Waga C, Hachiya Y, Kurihara E, Kumada S, Takeshita E, Nakagawa E, Inoue K, Miyatake S, Tsurusaki Y, Nakashima M, Saitsu H, Goto YI, Miyake N, Matsumoto N.
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Journal Title
Clin Genet.
Volume: 90(3)
Pages: 276-281
DOI
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations2016
Author(s)
Hamatani M, Jingami N, Tsurusaki Y, Shimada S, Shimojima K, Asada-Utsugi M, Yoshinaga K, Uemura N, Yamashita H, Uemura K, Takahashi R, Matsumoto N, Yamamoto T.
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Journal Title
J Hum Genet.
Volume: 61(10)
Pages: 899-902
DOI
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Clinical features of SMARCA2 duplication overlap with Coffin-Siris syndrome2016
Author(s)
Miyake N, Abdel-Salam G, Yamagata T, Eid MM, Osaka H, Okamoto N, Mohamed AM, Ikeda T, Afifi HH, Piard J, van Maldergem L, Mizuguchi T, Miyatake S, Tsurusaki Y, Matsumoto N.
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Journal Title
Am J Med Genet A.
Volume: 170 (10)
Pages: 2662-2670
DOI
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Whole exome sequence identified disease-causing CNVs of VPS13B responsible for Cohen syndrome in siblings with non-syndromic intellectual disability2016
Author(s)
Y. Enomoto, Y. Tsurusaki, T. Yokoi, M. Minatogawa, C. Hatano-Abe, K. Ida, T. Naruto, J. Mitsui, S. Tsuji, S. Morishita, K. Kurosawa
Organizer
American Society of Human Genetics 2016 Meeting
Place of Presentation
Vancouver (Canada)
Year and Date
2016-10-18 – 2016-10-22
Int'l Joint Research
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[Presentation] Cerebral vascular malformations in patients with ACTA2 mutations2016
Author(s)
C. Abe, T. Yokoi, M. Takagi, Y. Enomoto, Y. Tsurusaki, T. Naruto, T. Goto, H. Ueda, Y. Fujii, N. Aida, K. Kurosawa
Organizer
American Society of Human Genetics 2016 Meeting
Place of Presentation
Vancouver (Canada)
Year and Date
2016-10-18 – 2016-10-22
Int'l Joint Research
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[Presentation] A double mutation including a novel mutation of SLC9A9 gene and mosaic mutation of PORCN gene in a male patient with multiple congenital anomalies, intellectual disability, and autism spectrum disorder2016
Author(s)
M. Minatogawa, C. Abe, T. Yokoi, Y. Enomoto, K. Ida, Y. Tsurusaki, N. Harada, T. Naruto, K. Kurosawa
Organizer
American Society of Human Genetics 2016 Meeting
Place of Presentation
Vancouver (Canada)
Year and Date
2016-10-18 – 2016-10-22
Int'l Joint Research
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[Presentation] Early debelopment of rare tumors in individuals with congenital malformation syndrome2016
Author(s)
M. Minatogawa, F. Iwasaki, K. Fukuda, C. Hatano, T. Yokoi, Y. Enomoto, K. Ida, Y. Tsurusaki, N. Harada, T. Saito, J. Nagai, H. Goto, K. Kurosawa
Organizer
The 13th International Congress of Human Genetics in 2016
Place of Presentation
国立京都国際会館 (京都府京都市左京区)
Year and Date
2016-04-03 – 2016-04-07
Int'l Joint Research
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[Presentation] Low-prevalence somatic TSC2 mutations in sporadic lymphangioleiomyomatosis identified by deep-sequencing2016
Author(s)
A. Fujita, K. Ando, E. Kobayashi, K. Mitani, K. Okudera, M. Nakashima, S. Miyatake, Y. Tsurusaki, H. Saitsu, K. Seyama, N. Miyake, N. Matsumoto
Organizer
The 13th International Congress of Human Genetics in 2016
Place of Presentation
国立京都国際会館 (京都府京都市左京区)
Year and Date
2016-04-03 – 2016-04-07
Int'l Joint Research
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[Presentation] De novo DNM1 mutations in two cases of epileptic encephalopathy2016
Author(s)
M. Nakashima, T. Kouga, C. M. Lourenco, M. Shiina, T. Goto, Y. Tsurusaki, S. Miyatake, N. Miyake, H. Saitsu, K. Ogata, H. Osaka, N. Matsumoto
Organizer
The 13th International Congress of Human Genetics in 2016
Place of Presentation
国立京都国際会館 (京都府京都市左京区)
Year and Date
2016-04-03 – 2016-04-07
Int'l Joint Research
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[Presentation] De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing2016
Author(s)
H. Saitsu, T. Akita, J. Tohyama, H. Goldberg-Stern, Y. Kobayashi, R. Cohen, M. Kato, C. Ohba, S. Miyatake, Y. Tsurusaki, M. Nakashima, N. Miyake, A. Fukuda, N. Matsumoto
Organizer
The 13th International Congress of Human Genetics in 2016
Place of Presentation
国立京都国際会館 (京都府京都市左京区)
Year and Date
2016-04-03 – 2016-04-07
Int'l Joint Research
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