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The behavioral phenotype of the idic(15) syndrome

Postgraduate Medical School, University of Pisa, Italy.
American Journal of Medical Genetics Part C Seminars in Medical Genetics (Impact Factor: 3.54). 11/2010; 154C(4):448-55. DOI: 10.1002/ajmg.c.30281
Source: PubMed

ABSTRACT Idic(15) syndrome is a neurogenetic disorder clinically delineated by early central hypotonia, developmental delay and intellectual disability (ID), epilepsy, absent or very poor speech, and autistic or autistic-like behavior. It is due to the presence of a supernumerary marker chromosome formed by the inverted duplication of proximal chromosome 15, resulting in tetrasomy 15p and partial tetrasomy 15q, and containing the Prader-Willi/Angelman syndrome critical region (PWS/ASCR). The vast majority of these idic(15) derives from the two homologous maternal chromosomes at meiosis. To better define the behavior profile, we studied 22 idic(15) children (15 males and 7 females) observed at our institute between 1986 and 2010, and present, in detail, case studies of five of them. We have been able to perform standardized and semi-standardized measures of intelligence, and psychopathology in only 13 of our 22 patients, due to the limitations of chronological age, and to the severity of ID (ranging from mild-moderate, in 15%, to severe-profound, in 85% of our sample). The results show a distinct developmental profile in idic(15) patients, that may provide a behavioral signature for autism spectrum disorder (ASD)/ASD-like arising from the susceptibility locus on proximal 15q; and suggest that idic(15) individuals are not "true autistic," but distinct "autistic-like" persons with high score in the third ADOS-G and ADI-R area.

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    • "Another frequent pattern was the slow, but global evolution of the adaptive behavior, social interaction, and communicative skills over time. The aforementioned findings suggest " a distinct developmental profile, that may provide a behavioral signature for ASD/ASD-like arising from the susceptibility locus on proximal 15q " [Battaglia et al., 2010, p. 454]. The same authors eventually proposed that " idic(15) individuals are not " true autistic " , but distinct " autistic-like persons " . "
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    • "The idea that phenotypes are dependent on copy variants may not be correct and their underlying mechanisms are unlikely to be simple in humans. In contrast to the interstitial duplication of human chromosome 15q, termed idic (15) syndrome individuals, the presence of a supernumerary marker chromosome formed by the inverted duplication of proximal chromosome 15, resulting in partial tetrasomy 15q, often display increased, yet inappropriate, social behaviors (Battaglia et al. 2010). A gap between the mouse model and the human patient The mouse model for 15q duplication as an animal model for human neuropsychiatric disease fulfills construct validity, in which it possesses the same chromosomal abnormality as human patients. "
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