TY - JOUR T1 - <em>CTCF</em> deletion syndrome: clinical features and epigenetic delineation JF - Journal of Medical Genetics JO - J Med Genet SP - 836 LP - 842 DO - 10.1136/jmedgenet-2017-104854 VL - 54 IS - 12 AU - Ikumi Hori AU - Rie Kawamura AU - Kazuhiko Nakabayashi AU - Hidetaka Watanabe AU - Ken Higashimoto AU - Junko Tomikawa AU - Daisuke Ieda AU - Kei Ohashi AU - Yutaka Negishi AU - Ayako Hattori AU - Yoshitsugu Sugio AU - Keiko Wakui AU - Kenichiro Hata AU - Hidenobu Soejima AU - Kenji Kurosawa AU - Shinji Saitoh Y1 - 2017/12/01 UR - http://jmg.bmj.com/content/54/12/836.abstract 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. ER -