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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)637-648
Number of pages12
JournalHuman mutation
Volume38
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

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)

Cite this

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.

In: Human mutation, Vol. 38, No. 6, 01.06.2017, p. 637-648.

Research output: Contribution to journalArticle

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, vol. 38, no. 6, pp. 637-648. https://doi.org/10.1002/humu.23200
Imagawa E, Higashimoto K, Sakai Y, Numakura C, Okamoto N, Matsunaga S et al. Mutations in genes encoding polycomb repressive complex 2 subunits cause Weaver syndrome. Human mutation. 2017 Jun 1;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. In: Human mutation. 2017 ; Vol. 38, No. 6. pp. 637-648.
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AU - Higashimoto, Ken

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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

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