A novel PUS7 mutation causes intellectual disability with autistic and aggressive behaviors.
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ABSTRACT:
SUBMITTER: Darvish H
PROVIDER: S-EPMC6745718 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
A novel <i>PUS7</i> mutation causes intellectual disability with autistic and aggressive behaviors.
Darvish Hossein H Azcona Luis J LJ Alehabib Elham E Jamali Faezeh F Tafakhori Abbas A Ranji-Burachaloo Sakineh S Jen Joanna C JC Paisán-Ruiz Coro C
Neurology. Genetics 20190904 5
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Project description:We describe six patients from three families with three homozygous protein truncating variants in PUS7: c.89_90del, p.(Thr30Lysfs20*); c.1348C>T, p.(Arg450*); and a deletion of the penultimate exon 15. All patients 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 with slower walking speed and disorientation 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.
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