A Glutamine Repeat Variant of the RUNX2 Gene Causes Cleidocranial Dysplasia

Masaki Mastushita; Hiroshi Kitoh; Asli Subasioglu; Fatma Kurt Colak; Munis Dundar; Kenichi Mishima; Yoshihiro Nishida; Naoki Ishiguro

doi:10.1159/000370337

A Glutamine Repeat Variant of the RUNX2 Gene Causes Cleidocranial Dysplasia

Mol Syndromol. 2015 Feb;6(1):50-3. doi: 10.1159/000370337. Epub 2015 Jan 29.

Authors

Masaki Mastushita¹, Hiroshi Kitoh¹, Asli Subasioglu², Fatma Kurt Colak³, Munis Dundar³, Kenichi Mishima¹, Yoshihiro Nishida¹, Naoki Ishiguro¹

Affiliations

¹ Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Medical Genetics, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey.
³ Department of Medical Genetics, Erciyes University, Kayseri, Turkey.

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.

Keywords: Cleidocranial dysplasia; Glutamine repeat variant; Q/A domain; RUNX2.