TY - JOUR
T1 - MYT1L
T2 - A systematic review of genetic variation encompassing schizophrenia and autism
AU - Mansfield, Patricia
AU - Constantino, John N.
AU - Baldridge, Dustin
N1 - Funding Information:
Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development, the National Heart, Lung, and Blood Institute, and the National Human Genome Research Institute of the National Institutes of Health under Award Numbers U54HD087011 (the Intellectual and Developmental Disabilities Research Center at Washington University), K12HL120002, and K08HG010154. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development, the National Heart, Lung, and Blood Institute, and the National Human Genome Research Institute of the National Institutes of Health under Award Numbers U54HD087011 (the Intellectual and Developmental Disabilities Research Center at Washington University), K12HL120002, and K08HG010154. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 Wiley Periodicals, Inc.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - MYT1L
KW - autism
KW - reciprocal mutation
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85082966102&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.32781
DO - 10.1002/ajmg.b.32781
M3 - Review article
C2 - 32267091
AN - SCOPUS:85082966102
VL - 183
SP - 227
EP - 233
JO - American Journal of Medical Genetics - Neuropsychiatric Genetics
JF - American Journal of Medical Genetics - Neuropsychiatric Genetics
SN - 1552-4841
IS - 4
ER -