2017/01/19
Keio University School of Medicine
A joint research group—including Assistant Professor Kazuki Takeda of the Department of Orthopedic Surgery, Keio University School of Medicine (also of the Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences), Team Leader Shiro Ikegawa (RIKEN), Professor Morio Matsumoto and Senior Lecturer Kota Watanabe of the Department of Orthopedic Surgery, Keio University School of Medicine, the Japan Early Onset Scoliosis Research Group, and the Department of Genetics at Yokohama City University—has discovered that mutations in the TBX6 (T-box 6) gene are the cause of approximately 10% of Congenital Scoliosis (CS) cases in East Asian populations.
Scoliosis is a condition in which the spine curves, and the type caused by congenital vertebral malformations is called Congenital Scoliosis (CS). Its incidence is 0.5 to 1 per 1,000 births. Genetic factors are thought to be involved in the development of CS, and a worldwide search for causative genes has been underway. Recently, it has been reported that TBX6 is involved in the development of CS in Chinese populations. The joint research group analyzed the TBX6 gene in Japanese patients with CS and discovered not only the same mutation found in Chinese CS patients (a deletion of the TBX6 gene) but also novel mutations that have never been reported before. All of these were severe loss-of-function mutations, such as deletions, nonsense mutations, and frameshift mutations. Furthermore, by measuring gene expression levels using luciferase assays, the group also newly discovered that even missense mutations, which are considered relatively mild, can cause CS. Moreover, they clarified that spondylocostal dysostosis (SCD) with rib fusion, a more severe condition previously considered a separate group of disorders from CS, is part of a spectrum of diseases caused by TBX6 mutations.
This study, the first large-scale genetic analysis of CS in Japan, has revealed that 10% of CS cases, whose causes were previously unknown, are attributable to mutations in TBX6. It is expected that genetic testing for TBX6 will enable early diagnosis and treatment of CS in the future.
The findings were published in the online edition of "Human Mutation" on January 5 (January 6, Japan Standard Time) ahead of their inclusion in the print version, and are available for immediate media release.
For the full press release, please see below.