Naa15 Haploinsufficiency and De Novo Missense Variants Associate With Neurodevelopmental Disorders and Interfere With Neurogenesis and Neuron Development.
NAA15 gene faults derail early neuron wiring and may explain some cases of autism or global delay.
01Research in Context
What this study did
He et al. (2025) looked at the NAA15 gene in kids with autism and other delays.
They used lab dishes of growing neurons to see what happens when this gene breaks.
The team tested both total loss and small spelling changes of NAA15.
What they found
Broken NAA15 made too many baby neurons and weak links between them.
The result is a crowded, poorly wired brain sample.
This gives a clear cell-level story for why some kids have delays.
How this fits with other research
Barua et al. (2011) also traced autism risk to a single enzyme tweak, but in GLOI, not NAA15. Both papers show how tiny DNA changes can poison young neurons.
Sigar et al. (2023) scanned live kids and found messy whole-brain networks. Mei’s dish work helps explain how those networks start off wrong.
Napoli et al. (2018) found that kids with big DNA chunks missing often stay non-verbal. Mei’s study zooms deeper, showing one gene that can do similar harm.
Why it matters
You can’t fix genes in clinic yet, but you can add NAA15 to your genetic watch list. If parents ask about testing, you now have a concrete gene to discuss. Down the road, spotting this variant early could guide tighter motor and language targets from day one of therapy.
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02At a glance
03Original abstract
Neurodevelopmental disorders (NDDs) encompass a group of conditions that impact brain development and function, exhibiting significant genetic and clinical heterogeneity. NAA15, the auxiliary subunit of the N-terminal acetyltransferase complex, has garnered attention due to its association with NDDs. However, the precise role of NAA15 in cortical development and its contribution to NDDs remain elusive. By employing targeted sequencing on a large Chinese cohort affected by ASD and conducting an extensive literature review, we have compiled 64 distinct variants in the NAA15 gene identified among individuals with neurodevelopmental disorders. Our research demonstrates that loss of NAA15 leads to a substantial increase in neuronal count, potentially resulting in aberrant brain development and triggering repetitive as well as anxious behaviors in mice models. Furthermore, disorder-associated variants within NAA15 impair axon and synapse formation processes crucial for neural connectivity establishment. These findings shed light on the consequences of NAA15 deficiency along with its de novo mutations on brain development while unraveling the cellular mechanisms underlying NDDs.
Autism research : official journal of the International Society for Autism Research, 2025 · doi:10.1002/aur.3308