Loss-of-function mutations and global rearrangements in GPC3 in patients with Simpson-Golabi-Behmel syndrome

Keiko Shimojima; Yumiko Ondo; Eriko Nishi; Seiji Mizuno; Miharu Ito; Aya Ioi; Mariko Shimizu; Maho Sato; Masami Inoue; Nobuhiko Okamoto; Toshiyuki Yamamoto

doi:10.1038/hgv.2016.33

Loss-of-function mutations and global rearrangements in GPC3 in patients with Simpson-Golabi-Behmel syndrome

Hum Genome Var. 2016 Oct 13:3:16033. doi: 10.1038/hgv.2016.33. eCollection 2016.

Authors

Affiliations

¹ Tokyo Women's Medical University Institute for Integrated Medical Sciences , Tokyo, Japan.
² Department of Pediatrics, Central Hospital, Aichi Human Service Center , Kasugai, Japan.
³ Department of Pediatrics, Nagoya University Graduate School of Medicine , Nagoya, Japan.
⁴ Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health , Osaka, Japan.
⁵ Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health , Izumi, Japan.

Abstract

Simpson-Golabi-Behmel syndrome is a congenital malformation syndrome associated with mutations in GPC3, which is located in the Xq26 region. Three new loss-of-function mutations and a global X-chromosome rearrangement involving GPC3 were identified. A female sibling of the patient, who presented with a cleft palate and hepatoblastoma, carries the same chromosomal rearrangement and a paradoxical pattern of X-chromosome inactivation. These findings support variable GPC3 alterations, with a possible mechanism in female patients.