Relevance to Autism

A de novo LoF variant and a de novo likely damaging missense variant in the MYT1L gene were identified in two unrelated ASD probands from 2,270 trios screened by the Autism Sequencing Consortium in De Rubeis et al., 2017 (PMID 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in this report identified MYT1L as a gene meeting high statistical significance with a 0.05 < FDR 0.1, meaning that this gene had a 90% chance of being a true autism gene. De novo LoF variants in MYT1L were also identified in two sporadic cases in De Rocker et al., 2015: one in a patient presenting with ASD and intellectual disability, and the other in a patient presenting with intellectual disability and autistic features (PMID 25232846). Two additional de novo LoF variants in the MYT1L gene were identified in a Chinese ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016 (PMID 27824329), and an ASD proband from the ASD: Genomes to Outcome Study cohort in Yuen et al., 2017 (PMID 28263302). MYT1L has been proposed as a causative gene for intellectual disability and other phenotypes observed in cases with 2p25.3 deletions (PMID 21990140, 25232846). Copy number variants affecting the MYT1L gene have also been implicated in schizophrenia (Vrijenhoek et al., 2008; Lee et al., 2012; Van Den Bossche et al., 2013). A de novo protein-truncating variant in MYT1L was identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020; subsequent TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in this report identified MYT1L as a candidate gene with a false discovery rate (FDR) 0.01. Coursimault et al., 2021 described 40 previously unreported cases with pathogenic or likely pathogenic variants in the MYT1L gene; developmental delay, intellectual disability, and behavioral disorders were frequently observed in individuals with MYT1L variants, and a formal or informal diagnosis of autism spectrum disorder was made in 17/40 individuals (43%). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified MYT1L as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

May function as a panneural transcription factor associated with neuronal differentiation and may play a role in the development of neurons and oligodendroglia in the CNS.

External Links

References

Model Summary

Mytl1a or mytl1b knockdown zebrafish morphants manifested loss of oxytocin expression in the preoptic neuroendocrine area.

References