Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons.
Nora Urraca, Kevin Hope, A Kaitlyn Victor and 10 others
PMID 29423132WHAT IT FOUND
Lab neurons grown from baby tooth stem cells showed widespread gene expression changes in 15q duplication syndrome, especially lower levels of genes called FOXO1 and RORA, but few changes in Angelman deletion neurons.
This is a molecular clue, not a treatment result.
Key findings
01Neurons from 15q duplication samples showed 123 significantly different genes compared with controls, while Angelman deletion neurons showed 23.
02In 15q duplication neurons, FOXO1 transcript was reduced, and RORA protein was reduced in a separate set of six idic15q lines.
03Gene expression changes in 15q duplication neurons overlapped with increased gene expression seen in postmortem cortex from Dup15q and idiopathic autism.
STILL TO COME
How it was doneWhat they found
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What it does not show
The neurons were immature, only about 3 weeks old, and were a mixed neuron/glia culture rather than pure cortical neurons. Only nine subjects were used for the RNA sequencing comparison (3 controls, 3 Angelman deletion, 3 15q duplication), so the findings need replication in larger samples. The study measured gene expression in lab cells, not patient movement, communication, learning or therapy response. Most Angelman deletion neuron comparisons did not differ significantly from controls, so the result may not capture protein-level mechanisms. UBE3A expression was still detected in Angelman deletion neurons, which makes interpretation of that gene uncertain. The postmortem brain comparison was not a clinical diagnostic test and does not prove that these lab neurons model the patient's brain.
Declared interests
Funding was provided by the National Institute of Neurological Disorders and Stroke.
The easy way to misread this
Do not read this as evidence that a treatment works or that these gene changes diagnose a child's therapy needs. The study measured gene expression in immature lab neurons, not clinical outcomes.