Biallelic mutations in human DCC cause developmental split-brain syndrome
| العنوان: | Biallelic mutations in human DCC cause developmental split-brain syndrome |
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| المؤلفون: | May L. Griebel, Klaus Schmitz-Abe, Anh Thu N. Lam, Abdullah Abu Jamea, Caroline D. Robson, Mauricio R. Delgado, Sarah Servattalab, Mohammad Asif Dogar, Ibrahim A. Alorainy, A. James Barkovich, Maya Peeva, Saumya Shekhar Jamuar, Marie Drottar, Kyriacos Markianos, Khaled K. Abu-Amero, Zayed Al Zayed, Elizabeth C. Engle, P. Ellen Grant, Alissa M. D'Gama, Wai-Man Chan, Christopher A. Walsh, Nancy J. Clegg, Ed S. Lein, Timothy W. Yu, Wendy L. Ward, Thomas M. Bosley |
| المصدر: | Nature genetics |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Central Nervous System, Male, 0301 basic medicine, Loss of Heterozygosity, Receptors, Cell Surface, Scoliosis, Biology, Hippocampal formation, Polymorphism, Single Nucleotide, Mirror movements, Article, 03 medical and health sciences, 0302 clinical medicine, Intellectual Disability, Intellectual disability, Genetics, medicine, Humans, Agenesis of the corpus callosum, Neurons, Brain, Gene Expression Regulation, Developmental, Horizontal gaze palsy, Anatomy, Commissure, medicine.disease, Phenotype, 030104 developmental biology, Mutation, Female, Brainstem, Colorectal Neoplasms, 030217 neurology & neurosurgery |
| الوصف: | Motor, sensory, and integrative activities of the brain are coordinated by a series of midline-bridging neuronal commissures whose development is tightly regulated. Here we report a new human syndrome in which these commissures are widely disrupted, thus causing clinical manifestations of horizontal gaze palsy, scoliosis, and intellectual disability. Affected individuals were found to possess biallelic loss-of-function mutations in the gene encoding the axon-guidance receptor 'deleted in colorectal carcinoma' (DCC), which has been implicated in congenital mirror movements when it is mutated in the heterozygous state but whose biallelic loss-of-function human phenotype has not been reported. Structural MRI and diffusion tractography demonstrated broad disorganization of white-matter tracts throughout the human central nervous system (CNS), including loss of all commissural tracts at multiple levels of the neuraxis. Combined with data from animal models, these findings show that DCC is a master regulator of midline crossing and development of white-matter projections throughout the human CNS. |
| تدمد: | 1546-1718 1061-4036 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::810f6d374273cf3a5e7ec3c2d4ae6babTest https://doi.org/10.1038/ng.3804Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....810f6d374273cf3a5e7ec3c2d4ae6bab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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