Cross-level analysis of molecular and neurobehavioral function in a prospective series of patients with germline heterozygous PTEN mutations with and without autism.

The sample was small for a rare condition, with 61 analysed participants, so group differences and correlations could be unstable. Researchers could not examine whether molecular relationships were the same within each patient group. Only one time point was available, so the study could not show whether protein levels and neurobehavioral function were stable or changed over time. No brain or neural system measures were included, so blood protein levels were not linked directly to brain structure or function. Missing data were higher for attention (36%) and processing speed (28%), and were more common in younger children. No correction was made for multiple comparisons, because the analyses were preliminary. Protein measures came from blood-derived cells, and the paper did not establish that they fully reflect brain pathway activity. The murine comparison had substantial variability, especially in heterozygous mice.

Funding came from the National Institute of Neurological Disorders and Stroke, Ambrose Monell Foundation, Autism Speaks, and Hartwell Foundation. The supplied text does not include an author conflict-of-interest declaration.

Do not conclude that PTEN mutation status or blood protein levels can predict a patient's cognitive, language, motor, or adaptive outcome, or that pathway-targeted treatment works. The study was observational, the sample was small, and mutation status alone did not account for significant variance in neurobehavioral measures.