2. Academic Validation
  3. De novo SOX11 mutations cause Coffin-Siris syndrome

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

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.

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