The phenotypic manifestations of interstitial duplications of proximal 15qwith special reference to the autistic spectrum disorders

This study investigated the phenotypic manifestations of interstitial dupli cations of chromosome 15 that involve the Prader-Willi/Angelman syndrome cr itical region (PWACR). Twenty-one affected individuals from six families we re evaluated in detail, using standardized and semi-standardized measures o f intelligence, psychopathology, and physical anomalies. Special attention was placed on determining the prevalence of autism spectrum disorders as we ll as the relationship between the parental origin of the duplication and t he phenotypic effects. Assessments of the affected individuals were compare d with evaluations of the unaffected relatives from the same families. Resu lts indicated that duplications in the region were associated with variable degrees of intellectual impairments and motor coordination problems. Four of the subjects received a diagnosis of pervasive developmental disorder. T hree of these cases were probands and only one met criteria for classic aut ism. There was very little evidence of the duplication cosegregating with a utism spectrum disorder diagnosis. Paternally inherited duplications were s ignificantly less likely to give rise to phenotypic effects. The findings i ndicate that duplications in the PWACR give rise to developmental delay but not necessarily autism spectrum disorders. They also suggest that phenotyp ic expression is dependent on the parental origin of the duplication and im plicate maternally active genes in the pathogenesis of the developmental im pairments. Further research will be required to clarify the range and basis of the phenotypic manifestations. (C) 2001 Wiley-Liss, Inc.(dagger).