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Somatic mosaicism and neurodevelopmental disease

Nature Neurosciencevolume 21pages15041514 (2018) | Download Citation


Traditionally, we have considered genetic mutations that cause neurodevelopmental diseases to be inherited or de novo germline mutations. Recently, we have come to appreciate the importance of de novo somatic mutations, which occur postzygotically and are thus present in only a subset of the cells of an affected individual. The advent of next-generation sequencing and single-cell sequencing technologies has shown that somatic mutations contribute to normal and abnormal human brain development. Somatic mutations are one important cause of neuronal migration and brain overgrowth disorders, as suggested by visible focal lesions. In addition, somatic mutations contribute to neurodevelopmental diseases without visible lesions, including epileptic encephalopathies, intellectual disability, and autism spectrum disorder, and may contribute to a broad range of neuropsychiatric diseases. Studying somatic mutations provides insight into the mechanisms underlying human brain development and neurodevelopmental diseases and has important implications for diagnosis and treatment.

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The authors thank members of the Walsh laboratory for helpful discussions. A.M.D. was supported by the NIGMS (T32GM007753). C.A.W. was supported by the NINDS (R01NS079277), the NIMH (U01MH106883) through the Brain Somatic Mosaicism Network, the Allen Discovery Center program through The Paul G. Allen Frontiers Group, and the Manton Center for Orphan Disease Research. C.A.W. is an Investigator of the Howard Hughes Medical Institute.

Author information


  1. Division of Genetics and Genomics, Manton Center for Orphan Disease, and Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA, USA

    • Alissa M. D’Gama
    •  & Christopher A. Walsh
  2. Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA, USA

    • Alissa M. D’Gama
    •  & Christopher A. Walsh
  3. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    • Alissa M. D’Gama
    •  & Christopher A. Walsh


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The authors declare no competing interests.

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Correspondence to Christopher A. Walsh.

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