RT Journal Article SR Electronic T1 CTCF deletion syndrome: clinical features and epigenetic delineation JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 836 OP 842 DO 10.1136/jmedgenet-2017-104854 VO 54 IS 12 A1 Ikumi Hori A1 Rie Kawamura A1 Kazuhiko Nakabayashi A1 Hidetaka Watanabe A1 Ken Higashimoto A1 Junko Tomikawa A1 Daisuke Ieda A1 Kei Ohashi A1 Yutaka Negishi A1 Ayako Hattori A1 Yoshitsugu Sugio A1 Keiko Wakui A1 Kenichiro Hata A1 Hidenobu Soejima A1 Kenji Kurosawa A1 Shinji Saitoh YR 2017 UL http://jmg.bmj.com/content/54/12/836.abstract 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.