Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome

Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto

研究成果: ジャーナルへの寄稿記事

28 引用 (Scopus)

抄録

Weaver syndrome (WS) is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected WS by whole-exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c.707G>C, p.Arg236Thr) in EED (individual 2), and a missense mutation (c.1829A>T, p.Glu610Val) in SUZ12 (suppressor of zeste 12 homolog) (individual 3) inherited from her father (individual 4) with a mosaic mutation. SUZ12 is another component of PRC2 and germline mutations in SUZ12 have not been previously reported in humans. In vitro functional analyses demonstrated that the identified EED and SUZ12 missense mutations cause decreased trimethylation of lysine 27 of histone H3. These data indicate that loss-of-function mutations of PRC2 components are an important cause of WS.

元の言語英語
ページ(範囲)637-648
ページ数12
ジャーナルHuman mutation
38
発行部数6
DOI
出版物ステータス出版済み - 6 2017

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Polycomb Repressive Complex 2
Ectoderm
Embryonic Development
Missense Mutation
Mutation
Histones
Genes
Lysine
Exome
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Germ-Line Mutation
Fathers
Weaver syndrome
Enhancer of Zeste Homolog 2 Protein

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

これを引用

Imagawa, E., Higashimoto, K., Sakai, Y., Numakura, C., Okamoto, N., Matsunaga, S., ... Matsumoto, N. (2017). Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome. Human mutation, 38(6), 637-648. https://doi.org/10.1002/humu.23200

Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome. / Imagawa, Eri; Higashimoto, Ken; Sakai, Yasunari; Numakura, Chikahiko; Okamoto, Nobuhiko; Matsunaga, Satoko; Ryo, Akihide; Sato, Yoshinori; Sanefuji, Masafumi; Ihara, Kenji; Takada, Yui; Nishimura, Gen; Saitsu, Hirotomo; Mizuguchi, Takeshi; Miyatake, Satoko; Nakashima, Mitsuko; Miyake, Noriko; Soejima, Hidenobu; Matsumoto, Naomichi.

:: Human mutation, 巻 38, 番号 6, 06.2017, p. 637-648.

研究成果: ジャーナルへの寄稿記事

Imagawa, E, Higashimoto, K, Sakai, Y, Numakura, C, Okamoto, N, Matsunaga, S, Ryo, A, Sato, Y, Sanefuji, M, Ihara, K, Takada, Y, Nishimura, G, Saitsu, H, Mizuguchi, T, Miyatake, S, Nakashima, M, Miyake, N, Soejima, H & Matsumoto, N 2017, 'Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome', Human mutation, 巻. 38, 番号 6, pp. 637-648. https://doi.org/10.1002/humu.23200
Imagawa E, Higashimoto K, Sakai Y, Numakura C, Okamoto N, Matsunaga S その他. Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome. Human mutation. 2017 6;38(6):637-648. https://doi.org/10.1002/humu.23200
Imagawa, Eri ; Higashimoto, Ken ; Sakai, Yasunari ; Numakura, Chikahiko ; Okamoto, Nobuhiko ; Matsunaga, Satoko ; Ryo, Akihide ; Sato, Yoshinori ; Sanefuji, Masafumi ; Ihara, Kenji ; Takada, Yui ; Nishimura, Gen ; Saitsu, Hirotomo ; Mizuguchi, Takeshi ; Miyatake, Satoko ; Nakashima, Mitsuko ; Miyake, Noriko ; Soejima, Hidenobu ; Matsumoto, Naomichi. / Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome. :: Human mutation. 2017 ; 巻 38, 番号 6. pp. 637-648.
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abstract = "Weaver syndrome (WS) is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected WS by whole-exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c.707G>C, p.Arg236Thr) in EED (individual 2), and a missense mutation (c.1829A>T, p.Glu610Val) in SUZ12 (suppressor of zeste 12 homolog) (individual 3) inherited from her father (individual 4) with a mosaic mutation. SUZ12 is another component of PRC2 and germline mutations in SUZ12 have not been previously reported in humans. In vitro functional analyses demonstrated that the identified EED and SUZ12 missense mutations cause decreased trimethylation of lysine 27 of histone H3. These data indicate that loss-of-function mutations of PRC2 components are an important cause of WS.",
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AU - Imagawa, Eri

AU - Higashimoto, Ken

AU - Sakai, Yasunari

AU - Numakura, Chikahiko

AU - Okamoto, Nobuhiko

AU - Matsunaga, Satoko

AU - Ryo, Akihide

AU - Sato, Yoshinori

AU - Sanefuji, Masafumi

AU - Ihara, Kenji

AU - Takada, Yui

AU - Nishimura, Gen

AU - Saitsu, Hirotomo

AU - Mizuguchi, Takeshi

AU - Miyatake, Satoko

AU - Nakashima, Mitsuko

AU - Miyake, Noriko

AU - Soejima, Hidenobu

AU - Matsumoto, Naomichi

PY - 2017/6

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