Working together toward a cure
Publications by Others
Scientists' understanding of MYT1L is rapidly expanding, thanks to the dedication of a growing number of research teams around the world. The earliest publication describing MYT1L as a potential cause of intellectual disability and obesity appeared in 2011. Since then, multiple cohort studies and individual case reports have described people with MYT1L deletions, variants, and duplications. These reports have revealed both core characteristics of most people impacted by MYT1L differences and considerable diversity in the spectrum and severity of symptoms.
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More recently, research utilizing mouse models and cell lines has advanced our understanding of MYT1L-related neurodevelopmental disorders. Research teams in the U.S., Korea and Germany have developed mouse models with loss-of-function of the MYT1L gene, effectively mirroring clinical features observed in patients with MYT1L mutations, and cell lines have enabled complementary experiments not possible in mice. Mouse and cell lines serve as a critical foundation for preclinical testing of both pharmacologic and targeted gene-based therapies for MYT1L Syndrome. ​​Below, we list both publications that have been reviewed and vetted by the scientific community, as well as a handful of newly written papers (pre-prints) that are still under review.
Reviews (summaries of prior research)
2022: MYT1L in the making: emerging insights on functions of a neurodevelopmental disorder gene. Read Article
2020: MYT1L: A systematic review of genetic variation encompassing schizophrenia and autism. Read Article
Cohort Studies in Humans
Recognition of MYT1L as a cause of developmental disability and obesity began with publications in the early 2010s of groups of patients ("cohorts") sharing similar characteristics, and all possessing deletions that included the MYT1L gene. A pivotal retrospective cohort study in 2022 carefully described and compared characteristics of individuals with MYT1L deletions, nonsense variants, missense variants, and duplications, and identified the frequency of common symptoms such as intellectual disability and other learning differences, autism spectrum disorder, obesity or overweight, and epilepsy across these subgroups.
2023: 2p25.3 microduplications involving MYT1L: further phenotypic characterization through an assessment of 16 new cases and a literature review. Read Article
2022: MYT1L-associated neurodevelopmental disorder: description of 40 new cases and literature review of clinical and molecular aspects. Read Article
2020: Nine newly identified individuals refine the phenotype associated with MYT1L mutations. Read Article
2015: Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity. Read Article
2014: Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes. Read Article
2012: Microduplications disrupting the MYT1L gene (2p25.3) are associated with schizophrenia. Read Article
2011: MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions. Read Article
Mouse Studies
2025: Chromosomal and gonadal sex have differing effects on social motivation in mice.
2025: Lifespan in rodents with MYT1L heterozygous mutation. Read Article
2024 [preprint]: A survey of hypothalamic phenotypes identifies molecular and behavioral consequences of MYT1L haploinsufficiency in male and female mice. Read Article
2024: MYT1L deficiency impairs excitatory neuron trajectory during cortical development. Read Article
2023: MYT1L haploinsufficiency in human neurons and mice causes autism-associated phenotypes that can be reversed by genetic and pharmacologic intervention. Read Article
2023: MYT1L is required for suppressing earlier neuronal development programs in the adult mouse brain. Read Article
2022: Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice. Read Article
2022: Postnatal age-differential ASD-like transcriptomic, synaptic, and behavioral deficits in Myt1l-mutant mice. Read Article
2021: A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation. Read Article
2017: Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates. Read Article
Cell Line Studies
2025: Autism and Intellectual Disability-Associated MYT1L Mutation Alters Human Cortical Interneuron Differentiation, Maturation, and Physiology. Read Article
2021: Molecular Mechanisms Underlying Ascl1-Mediated Astrocyte-to-Neuron Conversion. Read Article
2019: Induced pluripotent stem cell line, ICAGi001-A, derived from human skin fibroblasts of a patient with 2p25.3 deletion and 2p25.3-p23.3 inverted duplication. Read Article
2018: Myt1l induced direct reprogramming of pericytes into cholinergic neurons. Read Article
2018: Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination. Read Article
2017: Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury. Read Article
2017: Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval
2p25.3 Region, MYT1L and Obesity
The MYT1L Gene is located on chromosome 2 in a region called "2p25.3". While studies indicate that MYT1L haploinsufficiency alone often causes obesity, another gene located in the 2p25.3 region, TMEM18, has also been linked to obesity. Thus, obesity in individuals with deletions that include both MYT1L and TMEM18 may be linked to either or both genes.
2022: Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice. Read Article
2021: A novel MYT1L mutation in a boy with syndromic obesity: Case report and literature review. Read Article
2021: A Genome-Wide Association Study of Childhood Body Fatness. Read Article
2020: The Obesity-Susceptibility Gene TMEM18 Promotes Adipogenesis through Activation of PPARG Read Article
2018: A novel MYT1L mutation in a patient with severe early-onset obesity and intellectual disability. Read Article
2018: Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity. Read Article
2017: Obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation. Read Article
2017: MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus. Read Article
Individual Case Reports
2023: MYT1L variant inherited by a mosaic father in a case of severe developmental and epileptic encephalopathy. Read Article
2023: Complex Autism Spectrum Disorder in a Patient with a Novel De Novo Heterozygous MYT1L Variant. Read Article
2021: A Japanese patient with a 2p25.3 terminal deletion presented with early-onset obesity, intellectual disability and diabetes mellitus: A case report. Read Article
2021: A novel MYT1L mutation in a boy with syndromic obesity: Case report and literature review. Read Article
2020: Mid-trimester fetal facial dysmorphology associated with 2p25.3 microdeletion. Read Article
2020: Mid-trimester fetal facial dysmorphology associated with 2p25.3 microdeletion. Read Article
2020: Mid-trimester fetal facial dysmorphology associated with 2p25.3 microdeletion. Read Article
2019: MYT1L mutation in a patient causes intellectual disability and early onset of obesity: a case report and review of the literature. Read Article
2018: A novel MYT1L mutation in a patient with severe early-onset obesity and intellectual disability. Read Article
2018: Disruptive Behavior, Global Developmental Delay, and Obesity in a 5-Year-Old Boy with a Chromosome Microduplication. Read Article
2015: Haploinsufficiency of the MYT1L gene causes intellectual disability frequently associated with behavioral disorder. Read Article
2014: A new patient with a terminal de novo 2p25.3 deletion of 1.9 Mb associated with early-onset of obesity, intellectual disabilities and hyperkinetic disorder. Read Article
2013: Monozygotic twins discordant for submicroscopic chromosomal anomalies in 2p25.3 region detected by array CGH. Read Article
2012: Germline mosaic transmission of a novel duplication of PXDN and MYT1L to two male half-siblings with autism. Read Article
ASO-Related Publications
2025: Innovations in RNA therapeutics: a review of recent advances and emerging technologies. Read Article
2025: Antisense oligonucleotide as novel therapies for neurogenetic disorders. Read Article
2024: Nucleic acid therapeutics: Past, present, and future. Read Article
2024: Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders. Read Article
2022: Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): II. Drugs in more advanced clinical development. Read Article
2021: Targeted Augmentation of Nuclear Gene Output (TANGO) of Scn1a rescues parvalbumin interneuron excitability and reduces seizures in a mouse model of Dravet Syndrome. Read Article
2021: Antisense oligonucleotide treatment rescues UBE3A expression and multiple phenotypes of an Angelman syndrome mouse model. Read Article
2020: Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression. Read Article
2020: TANGO With SCN1A: Can This Molecular Dance Defeat Dravet Syndrome?
Cell Line Studies
Cell line studies have been instrumental in elucidating the role of the MYT1L gene in neurodevelopmental disorders. Researchers have employed various cell models to investigate the consequences of MYT1L dysfunction.
Key findings from these studies include:
• Transcriptional Dysregulation: In a study published in PLOS Genetics, researchers created a human embryonic kidney (HEK) cell line with a null mutation in MYT1L using CRISPR-Cas9 technology. Gene expression profiling of this knockout cell line revealed that loss of MYT1L function leads to dysregulation of genes involved in neurodevelopmental processes. Notably, there was altered expression of genes associated with intellectual disability, suggesting that MYT1L plays a critical role in regulating neurodevelopmental gene networks.
• Neuronal Differentiation: Another study investigated the effects of MYT1L knockdown in human neural stem cells. The results indicated that reduced MYT1L expression impairs neuronal differentiation, highlighting its importance in maintaining neuronal identity and function. This study also identified a network of helix-loop-helix transcriptional regulators controlled by MYT1L, further emphasizing its role in neuronal development.
• Induced Neuronal (iN) Cells: MYT1L has been identified as a key factor in the direct reprogramming of fibroblasts into induced neuronal (iN) cells. The combination of three transcription factors—ASCL1, POU3F2/BRN2, and MYT1L—is sufficient to convert fibroblasts and other somatic cells into iN cells in vitro. MYT1L directly binds to specific DNA motifs on target gene promoters and represses transcription by recruiting a multiprotein complex containing SIN3B, thereby promoting neuronal identity.
These cell line studies have provided valuable insights into the molecular mechanisms by which MYT1L influences neuronal development and function.