@article{ref1,
title="Variants in PUS7 cause intellectual disability with speech delay, microcephaly, short stature, and aggressive behavior",
journal="American journal of human genetics",
year="2018",
author="de Brouwer, Arjan P. M. and Abou Jamra, Rami and Körtel, Nadine and Soyris, Clara and Polla, Daniel L. and Safra, Modi and Zisso, Avia and Powell, Christopher A. and Rebelo-Guiomar, Pedro and Dinges, Nadja and Morin, Violeta and Stock, Michael and Hussain, Mureed and Shahzad, Mohsin and Riazuddin, Saima and Ahmed, Zubair M. and Pfundt, Rolph and Schwarz, Franziska and de Boer, Lonneke and Reis, André and Grozeva, Detilina and Raymond, F. Lucy and Riazuddin, Sheikh and Koolen, David A. and Minczuk, Michal and Roignant, Jean-Yves and van Bokhoven, Hans and Schwartz, Schraga",
volume="103",
number="6",
pages="1045-1052",
abstract="We describe six persons from three families with three homozygous protein truncating variants in PUS7: c.89_90del (p.Thr30Lysfs<sup>∗</sup>20), c.1348C>T (p.Arg450<sup>∗</sup>), and a deletion of the penultimate exon 15. All these individuals have intellectual disability with speech delay, short stature, microcephaly, and aggressive behavior. PUS7 encodes the RNA-independent pseudouridylate synthase 7. Pseudouridylation is the most abundant post-transcriptional modification in RNA, which is primarily thought to stabilize secondary structures of RNA. We show that the disease-related variants lead to abolishment of PUS7 activity on both tRNA and mRNA substrates. Moreover, pus7 knockout in Drosophila melanogaster results in a number of behavioral defects, including increased activity, disorientation, and aggressiveness supporting that neurological defects are caused by PUS7 variants. Our findings demonstrate that RNA pseudouridylation by PUS7 is essential for proper neuronal development and function.<br><br>Copyright © 2018 American Society of Human Genetics. All rights reserved.<p /> <p>Language: en</p>",
language="en",
issn="0002-9297",
doi="10.1016/j.ajhg.2018.10.026",
url="http://dx.doi.org/10.1016/j.ajhg.2018.10.026"
}