title: Clinical impacts of genomic copy number gains at Xq28.
abstract: Duplications of the Xq28 region are the most frequent chromosomal aberrations observed in patients with intellectual disability (ID), especially in males. These duplications occur by variable mechanisms, including interstitial duplications mediated by segmental duplications in this region and terminal duplications (functional disomy) derived from translocation with other chromosomes. The most commonly duplicated region includes methyl CpG-binding protein 2 gene (MECP2), which has a minimal duplicated size of 0.2 Mb. Patients with MECP2 duplications show severe ID, intractable seizures and recurrent infections. Duplications in the telomeric neighboring regions, which include GDP dissociation inhibitor 1 gene (GDI1) and ras-associated protein RAB39B gene (RAB39B), are independently associated with ID, and many segmental duplications located in this region could mediate these frequently observed interstitial duplications. In addition, large duplications, including MECP2 and GDI1, induce hypoplasia of the corpus callosum. Abnormalities observed in the white matter, revealed by brain magnetic resonance imaging, are a common finding in patients with MECP2 duplications. As primary sequence analysis cannot be used to determine the region responsible for chromosomal duplication syndrome, finding this region relies on the collection of genotype-phenotype data from patients.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Toshiyuki
authors.identifier: 0000-0002-9484-3505
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences , Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Shimada
authors.affiliation: Department of Pediatric Neurology, Mikatahara General Hospital , Hamamatsu, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokochi
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders , Shizuoka, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Yoshitomi
authors.affiliation: Department of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health , Izumi, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders , Shizuoka, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health , Izumi, Japan .
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto