Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity

Fulltext:
165654.pdf
Embargo:
until further notice
Size:
5.585Mb
Format:
PDF
Description:
publisher's version
Publication year
2016Author(s)
Number of pages
11 p.
Source
Nature Genetics, 48, 8, (2016), pp. 877-887ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Molecular Animal Physiology
Human Genetics
Primary and Community Care
Cognitive Neuroscience
Radboudumc Extern
Neurology
Molecular Neurobiology
Journal title
Nature Genetics
Volume
vol. 48
Issue
iss. 8
Languages used
English (eng)
Page start
p. 877
Page end
p. 887
Subject
Molecular Animal Physiology; Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health SciencesAbstract
Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development.
This item appears in the following Collection(s)
- Academic publications [202738]
- Electronic publications [100845]
- Faculty of Medical Sciences [79998]
- Faculty of Science [31843]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.