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Kloosterman P.H.,Trent University | Summerfeldt L.J.,Trent University | Parker J.D.A.,Trent University | Holden J.J.A.,Queens University | Holden J.J.A.,Autism Research Program
Journal of Obsessive-Compulsive and Related Disorders | Year: 2013

The obsessive-compulsive behaviors central to Obsessive-Compulsive Disorder (OCD) are not uncommon in Autism Spectrum Disorders (ASD), however the association between these disorders is not yet clear. One construct which may be useful in delineating their overlapping characteristics is "Incompleteness" or a sense of things feeling "not just right". Incompleteness has been related to a constellation of symptoms in OCD, but its association with ASD has not yet been examined. In this study parents with two or more children with ASD (P-MC) (n=115) were compared to an independent sample of parents having a single child with an ASD (P-SC), matched by age and gender, on level of Incompleteness. Results indicate that P-MC parents scored significantly higher in Incompleteness than P-SC parents. Incompleteness scores were also associated with a profile of behaviors in their children with ASD (n=357) characterized by high scores on the empirically derived repetitive sensory motor actions and resistance to change domains of the Autism Diagnostic Interview-Revised (Cuccaro et al., 2003). We discuss the implications of Incompleteness found in parents of children with an ASD, as well as its utility as a possible endophenotype for both ASD and OCD. © 2013 Elsevier Ltd. Source


Liu X.,Queens University | Liu X.,Autism Research Program | Malenfant P.,Autism Research Program | Malenfant P.,Queens University | And 16 more authors.
European Journal of Human Genetics | Year: 2011

Reports of unrelated individuals with autism spectrum disorder (ASD) and similar clinical features having overlapping de novo interstitial deletions at 2p15-p16.1 suggest that this region harbors a gene(s) important to the development of autism. We molecularly characterized two such deletions, selecting two genes in this region, exportin 1 (XPO1) and orthodenticle homolog 1 (OTX1) for association studies in three North American cohorts (Autism Spectrum Disorder - Canadian American Research Consortium (ASD-CARC), New York, and Autism Genetic Resource Exchange (AGRE)) and one Italian cohort (Societ Italiana per la Ricerca e la Formazione sullAutismo (SIRFA)) of families with ASD. In XPO1, rs6735330 was associated with autism in all four cohorts (P0.05), being significant in ASD-CARC cohorts (P-value following false discovery rate correction for multiple testing (P FDR)1.29 × 10 5), the AGRE cohort (P FDR 0.0011) and the combined families (P FDR 2.34 × 10 9). Similarly, in OTX1, rs2018650 and rs13000344 were associated with autism in ASD-CARC cohorts (P FDR 8.65 × 10 7 and 6.07 × 10 5, respectively), AGRE cohort (P FDR 0.0034 and 0.015, respectively) and the combined families (P FDR 2.34 × 10 9 and 0.00017, respectively); associations were marginal or insignificant in the New York and SIRFA cohorts. A significant association (P FDR 2.63 × 10 11) was found for the rs2018650G-rs13000344C haplotype. The above three SNPs were associated with severity of social interaction and verbal communication deficits and repetitive behaviors (P-values 0.01). No additional deletions were identified following screening of 798 ASD individuals. Our results indicate that deletion 2p15-p16.1 is not commonly associated with idiopathic ASD, but represents a novel contiguous gene syndrome associated with a constellation of phenotypic features (autism, intellectual disability, craniofacial/CNS dysmorphology), and that XPO1 and OXT1 may contribute to ASD in 2p15-p16.1 deletion cases and non-deletion cases of ASD mapping to this chromosome region. © 2011 Macmillan Publishers Limited All rights reserved. Source


Noor A.,Center for Addiction and Mental Health | Whibley A.,University of Cambridge | Whibley A.,French Natural History Museum | Marshall C.R.,Applied Genomics | And 64 more authors.
Science Translational Medicine | Year: 2010

Autism is a common neurodevelopmental disorder with a complex mode of inheritance. It is one of the most highly heritable of the complex disorders, although the underlying genetic factors remain largely unknown. Here, we report mutations in the X-chromosome PTCHD1 (patched-related) gene in seven families with autism spectrum disorder (ASD) and in three families with intellectual disability. A 167-kilobase microdeletion spanning exon 1 was found in two brothers, one with ASD and the other with a learning disability and ASD features; a 90-kilobase microdeletion spanning the entire gene was found in three males with intellectual disability in a second family. In 900 probands with ASD and 208 male probands with intellectual disability, we identified seven different missense changes (in eight male probands) that were inherited from unaffected mothers and not found in controls. Two of the ASD individuals with missense changes also carried a de novo deletion at another ASD susceptibility locus (DPYD and DPP6), suggesting complex genetic contributions. In additional males with ASD, we identified deletions in the 5′ flanking region of PTCHD1 that disrupted a complex noncoding RNA and potential regulatory elements; equivalent changes were not found in male control individuals. Thus, our systematic screen of PTCHD1 and its 5′ flanking regions suggests that this locus is involved in ∼1% of individuals with ASD and intellectual disability. Source

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