CTCF deletion syndrome: Clinical features and epigenetic delineation

Ikumi Hori, Rie Kawamura, Kazuhiko Nakabayashi, Hidetaka Watanabe, Ken Higashimoto, Junko Tomikawa, Daisuke Ieda, Kei Ohashi, Yutaka Negishi, Ayako Hattori, Yoshitsugu Sugio, Keiko Wakui, Kenichiro Hata, Hidenobu Soejima, Kenji Kurosawa, Shinji Saitoh

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background Heterozygous mutations in CTCF have been reported in patients with distinct clinical features including intellectual disability. However, the precise pathomechanism underlying the phenotype remains to be uncovered, partly because of the diverse function of CTCF. Here we describe extensive clinical and genetic investigation for two patients with a microdeletion encompassing CTCF. Methods We performed genetic examination including comprehensive investigation of X chromosome inactivation and DNA methylation profiling at imprinted loci and genome-wide. Results Two patients showed comparable clinical features to those in a previous report, indicating that haploinsufficiency of CTCF was the major determinant of the microdeletion syndrome. Despite the haploinsufficiency of CTCF, X chromosome inactivation was normal. DNA methylation at imprinted loci was normal, but hypermethylation at CTCF binding sites was demonstrated, of which PRKCZ and FGFR2 were identified as candidate genes. Conclusions This study confirms that haploinsufficiency of CTCF causes distinct clinical features, and that a microdeletion encompassing CTCF could cause a recognisable CTCF deletion syndrome. Perturbed DNA methylation at CTCF binding sites, not at imprinted loci, may underlie the pathomechanism of the syndrome.

Original languageEnglish
Pages (from-to)836-842
Number of pages7
JournalJournal of Medical Genetics
Volume54
Issue number12
DOIs
Publication statusPublished - 01-12-2017

Fingerprint

Haploinsufficiency
DNA Methylation
Epigenomics
X Chromosome Inactivation
Binding Sites
DNA Fingerprinting
Intellectual Disability
Genome
Phenotype
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Hori, I., Kawamura, R., Nakabayashi, K., Watanabe, H., Higashimoto, K., Tomikawa, J., ... Saitoh, S. (2017). CTCF deletion syndrome: Clinical features and epigenetic delineation. Journal of Medical Genetics, 54(12), 836-842. https://doi.org/10.1136/jmedgenet-2017-104854
Hori, Ikumi ; Kawamura, Rie ; Nakabayashi, Kazuhiko ; Watanabe, Hidetaka ; Higashimoto, Ken ; Tomikawa, Junko ; Ieda, Daisuke ; Ohashi, Kei ; Negishi, Yutaka ; Hattori, Ayako ; Sugio, Yoshitsugu ; Wakui, Keiko ; Hata, Kenichiro ; Soejima, Hidenobu ; Kurosawa, Kenji ; Saitoh, Shinji. / CTCF deletion syndrome : Clinical features and epigenetic delineation. In: Journal of Medical Genetics. 2017 ; Vol. 54, No. 12. pp. 836-842.
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abstract = "Background Heterozygous mutations in CTCF have been reported in patients with distinct clinical features including intellectual disability. However, the precise pathomechanism underlying the phenotype remains to be uncovered, partly because of the diverse function of CTCF. Here we describe extensive clinical and genetic investigation for two patients with a microdeletion encompassing CTCF. Methods We performed genetic examination including comprehensive investigation of X chromosome inactivation and DNA methylation profiling at imprinted loci and genome-wide. Results Two patients showed comparable clinical features to those in a previous report, indicating that haploinsufficiency of CTCF was the major determinant of the microdeletion syndrome. Despite the haploinsufficiency of CTCF, X chromosome inactivation was normal. DNA methylation at imprinted loci was normal, but hypermethylation at CTCF binding sites was demonstrated, of which PRKCZ and FGFR2 were identified as candidate genes. Conclusions This study confirms that haploinsufficiency of CTCF causes distinct clinical features, and that a microdeletion encompassing CTCF could cause a recognisable CTCF deletion syndrome. Perturbed DNA methylation at CTCF binding sites, not at imprinted loci, may underlie the pathomechanism of the syndrome.",
author = "Ikumi Hori and Rie Kawamura and Kazuhiko Nakabayashi and Hidetaka Watanabe and Ken Higashimoto and Junko Tomikawa and Daisuke Ieda and Kei Ohashi and Yutaka Negishi and Ayako Hattori and Yoshitsugu Sugio and Keiko Wakui and Kenichiro Hata and Hidenobu Soejima and Kenji Kurosawa and Shinji Saitoh",
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Hori, I, Kawamura, R, Nakabayashi, K, Watanabe, H, Higashimoto, K, Tomikawa, J, Ieda, D, Ohashi, K, Negishi, Y, Hattori, A, Sugio, Y, Wakui, K, Hata, K, Soejima, H, Kurosawa, K & Saitoh, S 2017, 'CTCF deletion syndrome: Clinical features and epigenetic delineation', Journal of Medical Genetics, vol. 54, no. 12, pp. 836-842. https://doi.org/10.1136/jmedgenet-2017-104854

CTCF deletion syndrome : Clinical features and epigenetic delineation. / Hori, Ikumi; Kawamura, Rie; Nakabayashi, Kazuhiko; Watanabe, Hidetaka; Higashimoto, Ken; Tomikawa, Junko; Ieda, Daisuke; Ohashi, Kei; Negishi, Yutaka; Hattori, Ayako; Sugio, Yoshitsugu; Wakui, Keiko; Hata, Kenichiro; Soejima, Hidenobu; Kurosawa, Kenji; Saitoh, Shinji.

In: Journal of Medical Genetics, Vol. 54, No. 12, 01.12.2017, p. 836-842.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CTCF deletion syndrome

T2 - Clinical features and epigenetic delineation

AU - Hori, Ikumi

AU - Kawamura, Rie

AU - Nakabayashi, Kazuhiko

AU - Watanabe, Hidetaka

AU - Higashimoto, Ken

AU - Tomikawa, Junko

AU - Ieda, Daisuke

AU - Ohashi, Kei

AU - Negishi, Yutaka

AU - Hattori, Ayako

AU - Sugio, Yoshitsugu

AU - Wakui, Keiko

AU - Hata, Kenichiro

AU - Soejima, Hidenobu

AU - Kurosawa, Kenji

AU - Saitoh, Shinji

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background Heterozygous mutations in CTCF have been reported in patients with distinct clinical features including intellectual disability. However, the precise pathomechanism underlying the phenotype remains to be uncovered, partly because of the diverse function of CTCF. Here we describe extensive clinical and genetic investigation for two patients with a microdeletion encompassing CTCF. Methods We performed genetic examination including comprehensive investigation of X chromosome inactivation and DNA methylation profiling at imprinted loci and genome-wide. Results Two patients showed comparable clinical features to those in a previous report, indicating that haploinsufficiency of CTCF was the major determinant of the microdeletion syndrome. Despite the haploinsufficiency of CTCF, X chromosome inactivation was normal. DNA methylation at imprinted loci was normal, but hypermethylation at CTCF binding sites was demonstrated, of which PRKCZ and FGFR2 were identified as candidate genes. Conclusions This study confirms that haploinsufficiency of CTCF causes distinct clinical features, and that a microdeletion encompassing CTCF could cause a recognisable CTCF deletion syndrome. Perturbed DNA methylation at CTCF binding sites, not at imprinted loci, may underlie the pathomechanism of the syndrome.

AB - Background Heterozygous mutations in CTCF have been reported in patients with distinct clinical features including intellectual disability. However, the precise pathomechanism underlying the phenotype remains to be uncovered, partly because of the diverse function of CTCF. Here we describe extensive clinical and genetic investigation for two patients with a microdeletion encompassing CTCF. Methods We performed genetic examination including comprehensive investigation of X chromosome inactivation and DNA methylation profiling at imprinted loci and genome-wide. Results Two patients showed comparable clinical features to those in a previous report, indicating that haploinsufficiency of CTCF was the major determinant of the microdeletion syndrome. Despite the haploinsufficiency of CTCF, X chromosome inactivation was normal. DNA methylation at imprinted loci was normal, but hypermethylation at CTCF binding sites was demonstrated, of which PRKCZ and FGFR2 were identified as candidate genes. Conclusions This study confirms that haploinsufficiency of CTCF causes distinct clinical features, and that a microdeletion encompassing CTCF could cause a recognisable CTCF deletion syndrome. Perturbed DNA methylation at CTCF binding sites, not at imprinted loci, may underlie the pathomechanism of the syndrome.

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U2 - 10.1136/jmedgenet-2017-104854

DO - 10.1136/jmedgenet-2017-104854

M3 - Article

C2 - 28848059

AN - SCOPUS:85037042841

VL - 54

SP - 836

EP - 842

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

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