TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.

Nat Genet 2016 11 26;48(11):1359-1369. Epub 2016 Sep 26.

Aix Marseille Univ, CNRS, IBDM, Marseille, France.

TSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083212PMC
http://dx.doi.org/10.1038/ng.3681DOI Listing
November 2016
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References

(Supplied by CrossRef)

JD Buxbaum et al.
Neuron 2012

NN Parikshak et al.
Cell 2013

MW State et al.
Science 2012

AJ Willsey et al.
Cell 2013

MK Belmonte et al.
J. Neurosci. 2004

KY Kwan et al.
Development 2012

JA Rosenfeld et al.
PLoS One 2009

JA Rosenfeld et al.
Genet. Med. 2010

K Wang et al.
Nature 2009

BJ O'Roak et al.
Science 2012

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