title: A Glutamine Repeat Variant of the RUNX2 Gene Causes Cleidocranial Dysplasia.
abstract: Cleidocranial dysplasia (CCD), an autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles and delayed closure of the cranial sutures, is caused by mutations of the runt-related transcription factor 2 (RUNX2) gene. The RUNX2 gene consists of a glutamine and alanine repeat domain (Q/A domain, 23Q/17A), a DNA-binding Runt domain and a proline/serine/threonine-rich domain. We report on a familial case of CCD with a novel mutation within the Q/A domain of the RUNX2 gene, which is an insertion in exon 1 (p.Q71_E72insQQQQ) representing the Q-repeat variant (27Q/17A). Functional analysis of the 27Q variant revealed abolished transactivation capacity of the mutated RUNX2 protein. This is the first case report that demonstrated a glutamine repeat variant of the RUNX2 gene causes CCD.
authors: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Masaki
authors: M
authors: Mastushita
authors: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hiroshi
authors: H
authors: Kitoh
authors: Department of Medical Genetics, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey.
authors: Asli
authors: A
authors: Subasioglu
authors: Department of Medical Genetics, Erciyes University, Kayseri, Turkey.
authors: Fatma
authors: F
authors: Kurt Colak
authors: Department of Medical Genetics, Erciyes University, Kayseri, Turkey.
authors: Munis
authors: M
authors: Dundar
authors: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Kenichi
authors: K
authors: Mishima
authors: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yoshihiro
authors: Y
authors: Nishida
authors: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Naoki
authors: N
authors: Ishiguro
keywords: Cleidocranial dysplasia; Glutamine repeat variant; Q/A domain; RUNX2