col4a1 mutations cause ocular dysgenesis, neuronal localization defects, and myopathy in mice and walker-warburg syndrome in humanscol4a1突变引起眼部发育不全,神经元定位缺陷,和肌病在小鼠和人类walker-warburg综合症.pdfVIP

COL4A1 Mutations Cause Ocular Dysgenesis, Neuronal Localization Defects, and Myopathy in Mice and Walker- Warburg Syndrome in Humans 1. 1.¤ 1 1 Cassandre Labelle-Dumais , David J. Dilworth , Emily P. Harrington , Michelle de Leau , David 1 2 3 4 3 Lyons , Zhyldyz Kabaeva , M. Chiara Manzini , William B. Dobyns , Christopher A. Walsh , Daniel E. 2 1 Michele , Douglas B. Gould * 1 Departments of Ophthalmology and Anatomy, Institute for Human Genetics, University of California San Francisco School of Medicine, San Francisco, California, United States of America, 2 Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America, 3 Division of Genetics and The Manton Center for Orphan Disease Research, Children’s Hospital Boston, Howard Hughes Medical Institute, and Harvard Medical School, Boston, Massachusetts, United States of America, 4 Departments of Human Genetics, Neurology, and Pediatrics, University of Chicago, Chicago, Illinois, United States of America Abstract Muscle-eye-brain disease (MEB) and Walker Warburg Syndrome (WWS) belong to a spectrum of autosomal recessive diseases characterized by ocular dysgenesis, neuronal migration defects, and congenital muscular dystrophy. Until now, the pathophysiology of MEB/WWS has been attributed to alteration in dystroglycan post-translational modification. Here, we provide evidence that mutations in a gene coding for a major basement membrane protein, collagen IV alpha 1 (COL4A1), are a novel cause of MEB/WWS. Using a combination of histological, molecular, an