Parsing phenotypes in people with shared autism-linked variants; and more

Pulling threads: A new study describes how genetic background can influence neurodevelopmental phenotypes linked to a particular gene variant. To wit, when a parent and child both carry the 16p12.1 deletion, they often experience different clinical presentations. The researchers evaluated 17 classes of secondary variants and identified those that influenced risk for specific traits, such as neurological issues. In addition, the relationship between genotype and phenotype varied depending on inclusion criteria for a study population, further complicating this kind of network analysis. Cell

Rescue mission: Boosting levels of the protein ASCC3, which regulates ribosomes, may reverse impairments linked to fragile X syndrome, according to a new paper. The investigators used a modified form of CRISPR to demonstrate this novel therapeutic strategy. In the process, they better define the links between cellular processes and the FMRP protein, which is key to the syndrome. Last week, The Transmitter covered another novel CRISPR therapy approach, targeting the consequences of SCN2A haploinsufficiency. Science Translational Medicine

More autism research we spotted:

• “A precision health approach to medication management in neurodevelopmental conditions: A model development and validation study using four international cohorts” medRxiv
• “Human brain organoids record the passage of time over multiple years in culture” bioRxiv
  See also: “Brain ‘chimeroids’ reveal person-to-person differences rooted in genetics”
• “Activity deprivation modulates the SHANK3/HOMER1/mGluR5 signaling pathway to enable synaptic upscaling” The Journal of Neuroscience
• “Restoration of NEXMIF expression rescues abnormalities in gene transcription, neuron maturation and autistic-like behaviors in NEXMIF knockout mice” Translational Psychiatry
• “Early white matter microstructure alterations in infants with Down syndrome” NeuroImage