De novo SOX11 mutations cause Coffin-Siris syndrome

  • Nat Commun. 2014 Jun 2;5:4011. doi: 10.1038/ncomms5011.
Yoshinori Tsurusaki  1 ,  Eriko Koshimizu  1 ,  Hirofumi Ohashi  2 ,  Shubha Phadke  3 ,  Ikuyo Kou  4 ,  Masaaki Shiina  5 ,  Toshifumi Suzuki  6 ,  Nobuhiko Okamoto  7 ,  Shintaro Imamura  8 ,  Michiaki Yamashita  8 ,  Satoshi Watanabe  9 ,  Koh-ichiro Yoshiura  9 ,  Hirofumi Kodera  10 ,  Satoko Miyatake  10 ,  Mitsuko Nakashima  10 ,  Hirotomo Saitsu  10 ,  Kazuhiro Ogata  5 ,  Shiro Ikegawa  4 ,  Noriko Miyake  10 ,  Naomichi Matsumoto  10
Affiliations
  • 1. 1] Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan [2].
  • 2. Division of Medical Genetics, Saitama Children's Medical Center, 2100 Magome, Iwatsuki 339-8551, Japan.
  • 3. Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Rd, Lucknow 226014, India.
  • 4. Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
  • 5. Department of Biochemistry, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
  • 6. 1] Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan [2] Department of Obstetrics and Gynecology, Juntendo University, Hongo 3-1-3, Bunkyo-ku, Tokyo 113-8431, Japan.
  • 7. Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi 594-1101, Japan.
  • 8. National Research Institute of Fisheries Science, 2-12-4 Fukuura, Kanazawa-ku, Yokohama 236-8648, Japan.
  • 9. Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
  • 10. Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
PMID: 24886874 DOI: 10.1038/ncomms5011
Abstract

Coffin-Siris syndrome (CSS) is a congenital disorder characterized by growth deficiency, intellectual disability, microcephaly, characteristic facial features and hypoplastic nails of the fifth fingers and/or toes. We previously identified mutations in five genes encoding subunits of the BAF complex, in 55% of CSS patients. Here we perform whole-exome Sequencing in additional CSS patients, identifying de novo SOX11 mutations in two patients with a mild CSS phenotype. sox11a/b knockdown in zebrafish causes brain abnormalities, potentially explaining the brain phenotype of CSS. SOX11 is the downstream transcriptional factor of the PAX6-BAF complex, highlighting the importance of the BAF complex and SOX11 transcriptional network in brain development.