Enigmatic missense mutations can cause disease via creation of nuclear export signals.

Disease-causing missense mutations that occur within structurally and functionally unannotated protein regions can guide researchers to new mechanisms of protein regulation and dysfunction. Here, we report that the thrombocytopenia-, myelodysplastic syndromes-, and leukemia-associated P214L mutation in the transcriptional regulator ETV6 creates an XPO1-dependent nuclear export signal to cause protein mislocalization. Strategies to disrupt XPO1 activity fully restore ETV6 P214L protein nuclear localization and transcription regulation activity.

Impulsive aggression with irritability and responsive to divalproex: a pediatric bipolar spectrum disorder phenotype?

Background: The objective of this retrospective chart review was to evaluate the phenomenology and response to divalproex in a sub-population of children admitted to an inpatient setting with severe impairing symptoms of irritability and aggression. In addition, we examined whether the symptomatology of this group was consistent with a pediatric divalproex-responsive bipolar spectrum disorder.

Methods: The charts of 46 child and adolescent patients with prominent impulsive aggression with irritability admitted to a crisis stabilization center were assessed retrospectively.

Treatment challenges and safety considerations for antipsychotic use in children and adolescents with psychoses.

With increased prescribing of psychotropic medications to children and adolescents, more attention should be given to the safety and tolerability of these drugs in this population. Compared with adults, children are especially vulnerable to adverse effects, including extrapyramidal symptoms (EPS), sedation, weight gain, and prolactin elevation. The prevalence of EPS is much higher in children treated with conventional antipsychotics than in those given atypical antipsychotics.