1. Fradin D, Cheslack-Postava K, Ladd-Acosta C, Newschaffer C, Chakravarti A, Arking DE, Feinberg A, Fallin MD. {{Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs}}. {PLoS One};5(9)
BACKGROUND: Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association. METHODS AND FINDINGS: We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE) and the National Institute of Mental Health (NIMH) autism repository. We report parametric (GH, Genehunter) and allele-sharing linkage (Aspex) results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LOD(GH) = 3.79, empirical p<0.005 and LOD(Aspex) = 2.96, p = 0.008), 15 (LOD(GH) = 3.09, empirical p<0.005 and LOD(Aspex) = 3.62, empirical p = 0.003) and 20 (LOD(GH) = 3.36, empirical p<0.005 and LOD(Aspex) = 3.38, empirical p = 0.006). CONCLUSIONS: These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism.
2. Ghanizaeh A. {{Leptin as a new approach for treatment for autism and epilepsy, a hypothesis with clinical implications}}. {Brain Dev} (Sep 3)
3. Gjevik E, Eldevik S, Fjaeran-Granum T, Sponheim E. {{Kiddie-SADS Reveals High Rates of DSM-IV Disorders in Children and Adolescents with Autism Spectrum Disorders}}. {J Autism Dev Disord} (Sep 8)
Prevalence of current comorbid DSM-IV disorders was assessed in a special school population of children and adolescents with ASD (N = 71, age 6.0-17.9 years), representing all cognitive levels and main ASD subgroups. Symptoms were assessed through parent interview and association to child characteristics was explored. Seventy-two percent was diagnosed with at least one comorbid disorder. Anxiety disorders (41%) and attention deficit/hyperactivity disorder (31%) were most prevalent. Obsessive-compulsive disorder was more common in older children, and oppositional defiant disorder/conduct disorder more prevalent in pervasive developmental disorder, not otherwise specified. Our results show high rates of comorbid DSM-IV disorders and underscore the importance of such evaluation in children ASD. However, diagnostic challenges are present and future research on the diagnostic validity of comorbid psychiatric disorders is needed.
4. Gomot M, Blanc R, Clery H, Roux S, Barthelemy C, Bruneau N. {{Candidate Electrophysiological Endophenotypes of Hyper-Reactivity to Change in Autism}}. {J Autism Dev Disord} (Sep 9)
Although resistance to change is a main feature of autism, the brain processes underlying this aspect of the disorder remain poorly understood. The aims of this study were to examine neural basis of auditory change-detection in children with autism spectrum disorders (ASD; N = 27) through electrophysiological patterns (MMN, P3a) and to test whether these are quantitatively related to intolerance of change (using the BSE-R scale). ASD displayed significantly shorter MMN latency and larger P3a than controls, indicating a greater tendency to switch attention to deviant events. These electrophysiological abnormalities were significantly more marked in children who displayed greater difficulties in tolerating change. The atypical neurophysiological mechanism of change perception identified might thus be associated with one of the hallmark behavioural manifestations of autism.
5. Quintero-Rivera F, Sharifi-Hannauer P, Martinez-Agosto JA. {{Autistic and psychiatric findings associated with the 3q29 microdeletion syndrome: Case report and review}}. {Am J Med Genet A} (Sep 9)
The screening of individuals with mild dysmorphic features and mental retardation using whole genome scanning technologies has resulted in the delineation of several previously unrecognized microdeletion syndromes. Microdeletion of 3q29 has been recently described as one such new syndrome. The clinical phenotype is variable despite an almost identical submicroscopic deletion size in most cases. We report on two individuals that further expand the clinical presentation of this rare disorder and compare the findings with earlier reports to refine the 3q29 microdeletion syndrome phenotype. The propositi are a 10-year-old female and a 15-year-old male, who have in common intellectual disabilities, a history of autism and psychiatric symptoms ranging from bipolar disorder presenting with increasing suicidal ideation to aggressive behavior and general anxiety. Other shared physical findings include asymmetric face, high-nasal bridge, crowded/dysplastic teeth, and tapered fingers. Oligonucleotide array-based chromosomal microarray analysis (CMA) using a genome-wide SNP array identified a de novo subtelomeric microdeletion of chromosome region 3q29 ranging from 1.6 to 2.1 Mb. The region of overlap encompasses 20 RefSeq genes, including FBX045, DLG1, and PAK2. These genes are related to neuronal postsynaptic membrane function and PTEN signaling, suggesting a role for synaptic connectivity dysfunction in the etiology of autism in these children. The novel clinical presentation of our patients expands the clinical spectrum of the 3q29 microdeletion syndrome and provides additional insights into the pathophysiology of autism and psychiatric disorders. (c) 2010 Wiley-Liss, Inc.
6. Rodger S, Vishram A. {{Mastering Social and Organization Goals: Strategy Use by Two Children with Asperger Syndrome during Cognitive Orientation to Daily Occupational Performance}}. {Phys Occup Ther Pediatr} (Sep 7)
ABSTRACT Preliminary data supports the effectiveness of Cognitive Orientation to (daily) Occupational Performance (CO-OP) for children with Asperger syndrome (AS). Children with AS often experience social and organizational difficulties spanning daily occupations. This case study explored the pattern of Global Strategies and Domain-Specific Strategies (DSS) use, the type of guidance, and dimensions of time on task used by two children with AS (aged 10 and 12 years) in addressing social and organizational goals during the CO-OP intervention. Coding of the videotaped CO-OP sessions suggested that both children (a) utilized all the Global strategies, particularly « understanding the context » and « plan »; (b) used six common DSS, namely transitional supports, affective supports, attending, task-specification, task modification, and supplementing task knowledge, with task-specification being most prominent; (c) required minimal guidance while « doing »; and (d) engaged in considerable time « talking about the task. » The results provide initial insights into strategies that may enable children with AS to achieve social and organizational goals.
