In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 10 ( 2023-10-3), p. e0291978-
Abstract:
Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children (“primary” stereotypies, pCMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with pCMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. Exploratory gene ontology and network analyses highlight functional convergence in calcium ion transport, demethylation, cell signaling, cell cycle and development. Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0291978
DOI:
10.1371/journal.pone.0291978.g001
DOI:
10.1371/journal.pone.0291978.g002
DOI:
10.1371/journal.pone.0291978.t001
DOI:
10.1371/journal.pone.0291978.t002
DOI:
10.1371/journal.pone.0291978.s001
DOI:
10.1371/journal.pone.0291978.s002
DOI:
10.1371/journal.pone.0291978.s003
DOI:
10.1371/journal.pone.0291978.s004
DOI:
10.1371/journal.pone.0291978.s005
DOI:
10.1371/journal.pone.0291978.s006
DOI:
10.1371/journal.pone.0291978.s007
DOI:
10.1371/journal.pone.0291978.s008
DOI:
10.1371/journal.pone.0291978.s009
DOI:
10.1371/journal.pone.0291978.s010
DOI:
10.1371/journal.pone.0291978.s011
DOI:
10.1371/journal.pone.0291978.s012
DOI:
10.1371/journal.pone.0291978.s013
DOI:
10.1371/journal.pone.0291978.s014
DOI:
10.1371/journal.pone.0291978.r001
DOI:
10.1371/journal.pone.0291978.r002
DOI:
10.1371/journal.pone.0291978.r003
DOI:
10.1371/journal.pone.0291978.r004
DOI:
10.1371/journal.pone.0291978.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
Permalink