一个国际科研小组7月24日在新一期美国《科学》（Science）杂志上发表报告说，他们找到了导致眼球后退综合症的特定基因变异，这可能有助于开发治疗这种先天性眼球运动障碍的基因疗法。

　　眼球后退综合症患者出生后眼球运动受限并伴有眼球后退，眼球不能正常向外侧或内侧转动。医学界曾猜测这种疾病可能是控制眼球运动的肌肉存在缺陷造成的。

　　英国和美国科学家的新研究显示，导致眼球后退综合症的罪魁祸首是一种名为CHN1的基因。当这种基因变异时，它负责编码的一种蛋白质工作将出现异常。早先的研究已经知道，这种蛋白质在胚胎阶段对于发育中的神经纤维定位自己所要负责控制的眼球肌肉非常重要。

　　眼球后退综合症患者一般会出现视力问题，大多数患者都是到了几岁时才被诊断出来。全世界大约有数百万人患有这种疾病。

　　英国半岛医学院专家约翰·奇尔顿说，通过了解CHN1基因如何诱发眼球后退综合症，研究人员就能更加全面地理解胚胎阶段时视觉系统是如何发育的，在此基础上有可能更好地诊断这种疾病，甚至开发出针对它的基因疗法。（生物谷Bioon.com）

　　生物谷推荐原始出处：

　　Science，DOI: 10.1126/science.1156121，Noriko Miyake，Elizabeth C. Engle

　　Human CHN1 Mutations Hyperactivate 2-Chimaerin and Cause Duane’s Retraction Syndrome

　　Noriko Miyake 1, John Chilton 2, Maria Psatha 3, Long Cheng 1, Caroline Andrews 4, Wai-Man Chan 5, Krystal Law 5, Moira Crosier 6, Susan Lindsay 6, Michelle Cheung 3, James Allen 2, Nick J Gutowski 7, Sian Ellard 8, Elizabeth Young 9, Alessandro Iannaccone 10, Binoy Appukuttan 11, J. Timothy Stout 11, Stephen Christiansen 12, Maria Laura Ciccarelli 13, Alfonso Baldi 14, Mara Campioni 14, Juan C. Zenteno 15, Dominic Davenport 3, Laura E. Mariani 16, Mustafa Sahin 17, Sarah Guthrie 3, Elizabeth C. Engle 18*

　　1 Department of Medicine (Genetics), Children’s Hospital Boston, Boston, MA 02115, USA.; Harvard Medical School, Boston, MA 02115, USA.

　　2 Institute of Biomedical and Clinical Science, Peninsula Medical School, Research Way, Plymouth PL6 8BU, UK.

　　3 MRC Centre for Developmental Neurobiology, King’s College, Guy’s Campus, London SE1 1UL, UK.

　　4 Department of Medicine (Genetics), Children’s Hospital Boston, Boston, MA 02115, USA.; Harvard Medical School, Boston, MA 02115, USA.; Department of Neurology, Children’s Hospital Boston, Boston, MA 02115, USA.

　　5 Department of Medicine (Genetics), Children’s Hospital Boston, Boston, MA 02115, USA.

　　6 MRC-Wellcome Trust Human Developmental Biology Resource (Newcastle), Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne NE1 3BZ, UK.

　　7 Department of Neurology, Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon EX2 5DW, UK.; Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK.

　　8 Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK.; Department of Molecular Genetics, Royal Devon and Exeter Hospital, Barrack Road, Exeter, Devon EX2 5DW, UK.

　　9 Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK.

　　10 University of Tennessee Health Science Center, Hamilton Eye Institute, 930 Madison Avenue, Suite 731, Memphis, TN 38163, USA.

　　11 Casey Eye Institute, Oregon Health and Science University, 3375 SW Terwilliger Boulevard, Portland, OR 97239, USA.

　　12 Department of Ophthalmology, University of Minnesota, MMC 493, 420 Delaware Street SE, Minneapolis, MN 55455, USA.

　　13 Fatebenefratelli Hospital, Division of Ophthalmology, Isola Tiberina, Rome, Italy.

　　14 Department of Biochemistry "F. Cedrangolo," Section of Pathologic Anatomy, Second University of Naples, Naples, Italy.

　　15 Department of Genetics and Research Unit, Institute of Ophthalmology "Conde de Valenciana," Mexico City, Mexico.

　　16 Department of Neurology, Children’s Hospital Boston, Boston, MA 02115, USA.

　　17 Harvard Medical School, Boston, MA 02115, USA.; Department of Neurology, Children’s Hospital Boston, Boston, MA 02115, USA.

　　18 Department of Medicine (Genetics), Children’s Hospital Boston, Boston, MA 02115, USA.; Harvard Medical School, Boston, MA 02115, USA.; Department of Neurology, Children’s Hospital Boston, Boston, MA 02115, USA.; Department of Ophthalmology, Children’s Hospital Boston, Boston, MA 02115, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

　　* To whom correspondence should be addressed.

　　Elizabeth C. Engle , E-mail: [email protected]

　　These authors contributed equally to this work.

　　Deceased.

　　Duane’s retraction syndrome (DRS) is a complex congenital eye movement disorder caused by aberrant innervation of the extraocular muscles by axons of brainstem motor neurons. Studying families with a variant form of the disorder (DURS2-DRS), we have identified causative heterozygous missense mutations in CHN1, a gene on chromosome 2q31 that encodes 2-chimaerin, a RacGAP signaling protein previously implicated in the pathfinding of corticospinal axons in mice. We show that these are gain-of-function mutations that increase 2-chimaerin RacGAP activity in vitro. Several of the mutations appear to enhance 2-chimaerin translocation to the cell membrane or enhance its ability to self-associate. Expression of mutant 2-chimaerin constructs in chick embryos resulted in failure of oculomotor axons to innervate their target extraocular muscles. We conclude that 2-chimaerin has a critical developmental function in ocular motor axon pathfinding.