How to Cite this Article: Stevens SJC, van Ravenswaaij-Arts CMA, Janssen JWH, Klein Wassink-Ruiter JS, van Essen AJ, Dijkhuizen T, van Rheenen J, Heuts-Vijgen R, Stegmann APA, Smeets EEJGL, Engelen JJM. 2011. MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions. Am J Med Genet Part A 155: 2739–2745.
MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions†
Article first published online: 11 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 11, pages 2739–2745, November 2011
How to Cite
Stevens, S. J.C., van Ravenswaaij-Arts, C. M.A., Janssen, J. W.H., Klein Wassink-Ruiter, J. S., van Essen, A. J., Dijkhuizen, T., van Rheenen, J., Heuts-Vijgen, R., Stegmann, A. P.A., Smeets, E. E.J.G.L. and Engelen, J. J.M. (2011), MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions. Am. J. Med. Genet., 155: 2739–2745. doi: 10.1002/ajmg.a.34274
- Issue published online: 20 OCT 2011
- Article first published online: 11 OCT 2011
- Manuscript Accepted: 28 JUL 2011
- Manuscript Received: 17 FEB 2011
- intellectual disability;
- SNP array;
- deletion 2p25.3 (2pter);
A partial deletion of chromosome band 2p25.3 (2pter) is a rarely described cytogenetic aberration in patients with intellectual disability (ID). Using microarrays we identified deletions of 2p25.3, sized 0.37–3.13 Mb, in three adult siblings and three unrelated patients. All patients had ID, obesity or overweight and/or a square-shaped stature without overt facial dysmorphic features. Combining our data with phenotypic and genotypic data of three patients from the literature we defined the minimal region of overlap which contained one gene, i.e., MYT1L. MYT1L is highly transcribed in the mouse embryonic brain where its expression is restricted to postmitotic differentiating neurons. In mouse-induced pluripotent stem cell (iPS) models, MYT1L is essential for inducing functional mature neurons. These resemble excitatory cortical neurons of the forebrain, suggesting a role for MYT1L in development of cognitive functions. Furthermore, MYT1L can directly convert human fibroblasts into functional neurons in conjunction with other transcription factors. MYT1L duplication was previously reported in schizophrenia, indicating that the gene is dosage-sensitive and that shared neurodevelopmental pathways may be affected in ID and schizophrenia. Finally, deletion of MYT1, another member of the Myelin Transcription Factor family involved in neurogenesis and highly similar to MYT1L, was recently described in ID as well. The identification of MYT1L as candidate gene for ID justifies further molecular studies aimed at detecting mutations and for mechanistic studies on its role in neuron development and on neuropathogenic effects of haploinsufficiency. © 2011 Wiley Periodicals, Inc.