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1) Executive dysfunction is a recurrent, clinically important feature in Wolfram syndrome and may reflect WFS1-related cellular stress that perturbs neurotransmitter systems involved in planning, inhibition, and emotional regulation.
2) Molecular links between endoplasmic reticulum (ER) stress, mitochondrial signaling and circadian clocks provide biological plausibility for circadian dysregulation contributing to the neurobehavioral phenotype.
