science
Study Links X-Linked RNA to Autism Features in Males
Researchers identified deletions affecting the long non-coding RNA PTCHD1-AS in males with autism spectrum disorder. Mouse models lacking the RNA showed repetitive behaviors and social deficits without cognitive or ADHD-like symptoms.
May 18, 2:42 PM·1m read1 source
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A study published in Nature examined whole-genome sequencing data from 9,349 individuals with autism spectrum disorder and 8,332 controls. Researchers identified 27 males with ASD who carried X-chromosome microdeletions implicating the long non-coding RNA PTCHD1-AS.
01. The paper notes that established autism-linked genes are typically protein-coding and often involve broader cognitive or medical features.
Ptchd1-as knockout mouse models were created by disrupting the evolutionarily conserved exon 3. Male knockout mice displayed increased repetitive behaviors and impaired social behavior and communication. The mice did not show cognitive comorbidities or ADHD-like behaviors.
Hippocampus-dependent synaptic function, complex learning, and locomotor activity remained unaffected. Native Ptchd1-as showed sustained expression from postnatal day 7 onward in the dorsal striatum, a brain region implicated in autism. Multi-omics analysis revealed transcriptomic alterations in striatal oligodendrocytes, astrocytes, and neurons affecting myelination and synaptic plasticity.
Disrupting Ptchd1-as led to reductions in conventional protein kinase C isoforms, altered SRC and GSK-3α/β phosphorylation, and enhanced striatal synaptic plasticity including long-term potentiation and long-term depression. The findings suggest striatal molecular and circuit-level dysregulation through PTCHD1-AS may contribute to autism spectrum disorder etiology.
