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

Nature Genetics
Josefine S WitteveenSharon M Kolk


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.


Aug 31, 2000·Biochemical and Biophysical Research Communications·S KyrylenkoA Salminen
Apr 23, 2002·Nature Reviews. Neuroscience·Peter T Fox, Jack L Lancaster
Jan 3, 2004·Nature Neuroscience·Stephen C NoctorArnold R Kriegstein
Jun 25, 2004·Nucleic Acids Research·Bingbing YuanFran Lewitter
Nov 27, 2004·Current Genetics·Rebecca A Silverstein, Karl Ekwall
Apr 23, 2005·Human Brain Mapping·Peter T FoxJack L Lancaster
May 18, 2005·Neuroinformatics·Angela R LairdPeter T Fox
Aug 2, 2005·Molecular and Cellular Biology·Shaun M CowleyRobert N Eisenman
Aug 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Vardhan S DaniSacha B Nelson
Sep 17, 2005·Molecular and Cellular Biology·Shravanti RampalliSamit Chattopadhyay
Nov 30, 2005·Nature Reviews. Molecular Cell Biology·Magdalena Götz, Wieland B Huttner
Jul 22, 2006·Molecular and Cellular Neurosciences·Sharon Margriet KolkMaria J Donoghue
Dec 7, 2006·Neural Development·Flavio R ZolessiWilliam A Harris
Dec 8, 2006·Nature·Ed S LeinAllan R Jones
May 22, 2007·Nature Reviews. Neuroscience·Bradley J MolyneauxJeffrey D Macklis
Nov 9, 2007·Neuron·Maria Chahrour, Huda Y Zoghbi
Feb 22, 2008·The Journal of Comparative Neurology·Stephen C NoctorArnold R Kriegstein
May 30, 2008·Current Opinion in Neurobiology·Dino P LeoneSusan K McConnell
Aug 22, 2008·Journal of Cell Science·Jennifer L FishWieland B Huttner
Sep 9, 2008·The International Journal of Biochemistry & Cell Biology·Patrick McDonelBrian D Hendrich
Nov 11, 2008·Molecular Cell·Chris van OevelenBrian David Dynlacht
Jan 14, 2009·The Journal of Biological Chemistry·Gretchen A BaltusShilpa Kadam
Mar 20, 2009·The Journal of Comparative Neurology·Yumiko HatanakaMasayuki Masu
Oct 9, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sharon Margriet KolkR Jeroen Pasterkamp
Oct 15, 2009·Mechanisms of Development·Aishwarya Swaminathan, Lori A Pile
Nov 19, 2009·American Journal of Medical Genetics. Part a·Joris AndrieuxMuriel Holder-Espinasse
Jan 29, 2010·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Lorelei D Shoemaker, Paola Arlotta
Mar 20, 2010·Epilepsy & Behavior : E&B·Aglaia VignoliMaria Paola Canevini
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Francesco BedogniRobert F Hevner
Oct 5, 2010·Nature Genetics·Adeline K NicholasC Geoffrey Woods
May 27, 2011·In Vitro Cellular & Developmental Biology. Animal·Daniela E SuzukiOswaldo Keith Okamoto
Oct 18, 2011·Journal of Medical Genetics·Marjolein H WillemsenTjitske Kleefstra
Nov 9, 2011·Frontiers in Molecular Neuroscience·Sharon Margriet KolkGerard Julianus Maria Martens
Nov 22, 2011·Nature Cell Biology·Elisabete M NascimentoMichaela Frye
Dec 20, 2011·Journal of Medical Genetics·Heather C MeffordEvan E Eichler
Dec 31, 2011·Developmental Biology·Patrick McDonelBrian D Hendrich
Jan 6, 2012·Orphanet Journal of Rare Diseases·Pilar L Magoulas, Ayman W El-Hattab


Jan 19, 2020·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Yi LiuZhongtao Gai
Apr 16, 2019·The British Journal of Radiology·Sue Y YiJohn-Paul J Yu
Aug 13, 2020·American Journal of Medical Genetics. Part a·Linde C M van DongenJos I M Egger
Apr 30, 2020·Journal of Clinical Medicine·Victor Murcia PienkowskiRafał Płoski
Aug 21, 2019·Cold Spring Harbor Molecular Case Studies·Alejandro FerrerRalitza H Gavrilova
Feb 7, 2019·European Journal of Human Genetics : EJHG·Ohad WormserOhad S Birk
Nov 4, 2020·American Journal of Medical Genetics. Part a·Pelin Ercoskun, Cigdem Yuce Kahraman
Aug 5, 2019·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Wenmin SunQingjiong Zhang
Jan 14, 2021·European Journal of Human Genetics : EJHG·Meena BalasubramanianTjitske Kleefstra
Dec 18, 2018·Psychiatry Research. Neuroimaging·Paul A RowleyJohn-Paul J Yu

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