Variations in MYT1L, a gene encoding a transcription factor expressed in the brain, have been associated with autism, intellectual disability, and schizophrenia. Here we provide an updated review of published reports of neuropsychiatric correlates of loss of function and duplication of MYT1L. Of 27 duplications all were partial; 33% were associated exclusively with schizophrenia, and the chromosomal locations of schizophrenia-associated duplications exhibited a distinct difference in pattern-of-location from those associated with autism and/or intellectual disability. Of 51 published heterozygous loss of function variants, all but one were associated with intellectual disability, autism, or both, and one resulted in no neuropsychiatric diagnosis. There were no reports of schizophrenia associated with loss of function variants of MYT1L (Fisher's exact p <.00001, for contrast with all reported duplications). Although the precise function of the various mutations remains unspecified, these data collectively establish the candidacy of MYT1L as a reciprocal mutation, in which schizophrenia may be engendered by partial duplications, typically involving the 3′ end of the gene, while developmental disability—notably autism—is associated with both loss of function and partial duplication. Future research on the specific effects of contrasting mutations in MYT1L may provide insight into the causal origins of autism and schizophrenia.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number4
StatePublished - Jun 1 2020


  • MYT1L
  • autism
  • reciprocal mutation
  • schizophrenia


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