PRKCB1 Gene Variants Influence Stereotypic Behaviors in Autism-Spectrum Disorders

Background: Autism is a complex neurodevelopmental disorder, likely encompassing multiple pathogenetic components. Single genes most likely influence a single component, rather than the entire set of autistic signs and symptoms. We have recently shown in 245 ASD patients that at least four principal components provide major contributions to autism pathogenesis, namely (I) a disruption of the circadian cycle associated with behavioral and sensory abnormalities, (II) dysreactive immune processes underlying both prenatal obstetric complications and postnatal excessive body growth rates, (III) a generalized developmental delay linked in some way to a “leaky kidney”, and (IV) an abnormal serotoninergic modulation of neural circuits underlying stereotypies and mirror neuron-mediated social behaviors. PRKCB1 contributions to these components were assessed here.

Objectives: The purpose of this study is to assess whether the PRKCB1 gene variant associated with autism provides broad contributions to the pathogenesis of the disease or instead contributes to a specific component.

Methods: Marker variables from these 4 principal components were correlated with PRKCB1 genotypes at SNP rs3785392, previously found most associated with autistic disorder (Lintas et al, Mol Psychiatry E-pub March 4, 2008), in 201 ASD patients.

Results: The G allele at rs3785392 is significantly associated with the marker variable for component IV, verbal and vocal stereotypies (chi squared = 7.16, 2 df, P<0.05). Also motor stereotypies, another variable in component IV, display a non-significant trend in the same direction (chi squared = 4.53, 2 df, P=0.1). There is no association between rs3785392 and marker variables for components IA (sleep disorders), IB (hyperactivity), II (history of allergies) and III (level of verbal language development).

Conclusions: PRKCB1 gene variants associated with autism influence the disease phenotype in the area of component IV, especially in reference to stereotypic behaviors.