Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism.
Michael S Breen, Andrew Browne, Gabriel E Hoffman and 4 others
PMID 32560742WHAT IT FOUND
Neural cells grown from 7 people with Phelan-McDermid syndrome showed altered gene expression compared with 6 siblings, especially Wnt pathways.
No therapy was tested, so this does not change clinical practice.
Key findings
01Gene expression differed for 392 genes in neural progenitor cells and 82 genes in neurons in participants with Phelan-McDermid syndrome compared with unaffected siblings.
02Nine genes were changed in both cell types, including SHANK3, which was under-expressed in Phelan-McDermid syndrome.
03Under-expressed genes were enriched for Wnt signaling, and a separate neuron batch showed similar Wnt-related under-expression.
STILL TO COME
How it was doneWhat they found
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What it does not show
Only 13 participants were studied, and the neuron analyses used cells from 5 cases and 5 siblings, so the sample is small. The study measured gene expression in lab-grown cells, not walking, speech, behaviour, or therapy response. The authors state they could not validate the findings in independent biological samples because Phelan-McDermid syndrome is rare. Neuron cell type proportions were predicted from bulk gene expression, not directly counted, so some differences could reflect mixture changes. The authors note that the progenitor cells can drift toward a more posterior-like identity with repeated culture, although they used low-passage cells.
Declared interests
The supplied funding section names the Autism Science Foundation and the Beatrice and Samuel A. Seaver Foundation. It does not report author conflicts of interest.
The easy way to misread this
Do not read the Wnt signaling findings as evidence that a medication or therapy should be changed. The study measured gene expression in lab-grown cells from 13 participants, not symptoms, therapy response, or clinical outcomes.