Biallelic mutations in human DCC cause developmental split-brain syndrome
Nature Genetics 49, 606 (2017).
doi:10.1038/ng.3804
Authors: Saumya S Jamuar, Klaus Schmitz-Abe, Alissa M D'Gama, Marie Drottar, Wai-Man Chan, Maya Peeva, Sarah Servattalab, Anh-Thu N Lam, Mauricio R Delgado, Nancy J Clegg, Zayed Al Zayed, Mohammad Asif Dogar, Ibrahim A Alorainy, Abdullah Abu Jamea, Khaled Abu-Amero, May Griebel, Wendy Ward, Ed S Lein, Kyriacos Markianos, A James Barkovich, Caroline D Robson, P Ellen Grant, Thomas M Bosley, Elizabeth C Engle, Christopher A Walsh & Timothy W Yu
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 th...
Source: Nature Genetics - Category: Genetics & Stem Cells Authors: Saumya S Jamuar Klaus Schmitz-Abe Alissa M D'Gama Marie Drottar Wai-Man Chan Maya Peeva Sarah Servattalab Anh-Thu N Lam Mauricio R Delgado Nancy J Clegg Zayed Al Zayed Mohammad Asif Dogar Ibrahim A Alorainy Abdullah Abu Jamea Khaled Abu-Amero May Griebel Tags: Letter Source Type: research
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