MYT1L: A systematic review of genetic variation encompassing schizophrenia and autism
Open accessAbstract
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.
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Myt1L is a member of the Myt/NZF family, encodes a neuronal transcription factor with 6 zinc fingers, and its expression has only been found in brain tissue thus far.
“Myt1L is a member of the Myt/NZF family, which encodes a neuronal transcription factor with 6 zinc fingers. Its expression has only been found in brain tissue thus far [46].”
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- Authors
- Mansfield, P., Constantino, J. N., & Baldridge, D.
- Affiliations
- Saint Louis University (US)
- Washington University in St. Louis (US)
- Corresponding author
- Constantino, John N.
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2020-04-08
- Volume
- 183
- Issue
- 4
- Pages
- 227-233
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC7605444
- OpenAlex
- W3014311564
- Cited by
- 27
- References
- 43
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 3
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD087011)
- National Heart and Lung Institute (K12HL120002)
- National Human Genome Research Institute (K08HG010154)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- MYT1L, schizophrenia, autism spectrum disorder, intellectual disability, partial gene duplication, loss-of-function mutations, transcription factors, neuropsychiatric disorders, chromosomal location
- MeSH terms
- Autistic Disorder, Gene Expression Regulation, Humans, Intellectual Disability, Mutation, Nerve Tissue Proteins, Phenotype, Schizophrenia, Transcription Factors, Genetic Variation, Gene Deletion, Gene Duplication, Genetic Association Studies
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