Objective: Paternal deletion and maternal uniparental disomy are the principa l genetic subtypes associated with Prader- Willi syndrome (PWS). Recent clinica l findings suggest differences in phenotype between these subtypes. The present experimental study addresses this issue using a cognitive psycho- physiological setup. Methods: Behaviour and event- related brain activity (ERP) was recorded by a continuous performance response inhibition task (CPT- AX) in adults with paternal deletion PWS (n=11), maternal uniparental disomy PWS (n=11) and normal controls (n=11). The dependent behavioural variables of the CPT- AX task were r eaction time and correct scores. For the ERPs the N200 and P300 components were included which are related to early modality- specific inhibition and late gene ral inhibition, respectively. Results: The disomy group had fewer correct scores and increased reaction times as compared to the CPT- AX task than the control and deletion group. Both PWS subgroups differed significantly from the control g roup for the N200 amplitude. Only the control group showed the typical task modu lation for the N200 amplitude. The amplitude of the P300 component was considera bly smaller in the uniparental disomy group than in the deletion and control gro ups. Conclusions: The ERP results suggest that early modality specific inhibitio n is impaired in both PWS genetic subtypes. Late general inhibition is impaired in the uniparental disomy group only. Thus, although the ERP data suggests a com mon impairment in early visual inhibition processing, uniparental disomy and par ental deletion genetic PWS subtypes clearly differ in their behavioural and brai n activation phenotypes. Significance: The present study is the first experiment al demonstration which explains the two principal genetic mechanisms that hinder the expression of the genes at 15q11- q13g in PWS result in different behaviou ral phenotype.
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