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MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2011 Nov; Vol. 155A (11), pp. 2739-45. Date of Electronic Publication: 2011 Oct 11. - Publication Year :
- 2011
-
Abstract
- 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.<br /> (Copyright © 2011 Wiley Periodicals, Inc.)
- Subjects :
- Abnormal Karyotype
Adolescent
Adult
Body Mass Index
Child
Child, Preschool
Chromosomes, Human, Pair 2 metabolism
DNA-Binding Proteins metabolism
Female
Haploinsufficiency
Humans
In Situ Hybridization, Fluorescence
Infant
Intellectual Disability metabolism
Male
Metaphase
Middle Aged
Neurogenesis
Obesity genetics
Oligonucleotide Array Sequence Analysis
Overweight genetics
Polymorphism, Single Nucleotide
Transcription Factors metabolism
Chromosome Deletion
Chromosomes, Human, Pair 2 genetics
DNA-Binding Proteins genetics
Intellectual Disability genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 155A
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 21990140
- Full Text :
- https://doi.org/10.1002/ajmg.a.34274