1. Cukier HN, Rabionet R, Konidari I, Rayner-Evans MY, Baltos ML, Wright HH, Abramson RK, Martin ER, Cuccaro ML, Pericak-Vance MA, Gilbert JR. {{Novel variants identified in methyl-CpG-binding domain genes in autistic individuals}}. {Neurogenetics};2009 (Nov 18)
Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4. A total of 46 alterations were identified in the four genes, including ten missense changes and two deletions that alter coding sequence. Several are either unique to our autistic population or cosegregate with affected individuals within a family, suggesting a possible relation of these variations to disease etiology. Variants include a R23M alteration in two affected half brothers which falls within the MBD domain of the MBD3 protein, as well as a frameshift in MBD4 that is predicted to truncate almost half of the protein. These results suggest that rare cases of autism may be influenced by mutations in members of the dynamic MBD protein family.
2. Manning MM, Wainwright LD. {{The Role of High Level Play as a Predictor Social Functioning in Autism}}. {J Autism Dev Disord};2009 (Nov 17)
Play and social abilities of a group of children diagnosed with high functioning autism were compared to a second group diagnosed with a variety of developmental language disorders (DLD). The children with autism engaged in fewer acts of high level play. The children with autism also had significantly lower social functioning than the DLD group early in the play session; however, these differences were no longer apparent by the end of the play session. In addition, a significant association existed between play and social functioning regardless of diagnosis. This suggests that play may act as a current indicator of social ability while providing an arena for social skills practice.
3. Martin JS, Poirier M, Bowler DM. {{Brief Report: Impaired Temporal Reproduction Performance in Adults with Autism Spectrum Disorder}}.{ J Autism Dev Disord};2009 (Nov 19)
Although temporal processing has received little attention in the autism literature, there are a number of reasons to suspect that people with autism spectrum disorder (ASD) may have particular difficulties judging the passage of time. The present study tested a group of 20 high-functioning adults with ASD and 20 matched comparison participants on a temporal reproduction task. The ASD group made reproductions that were significantly further from the base durations than did the comparison group. They were also more variable in their responses. Furthermore the ASD group showed particular difficulties as the base durations increased, tending to underestimate to a much greater degree than the comparison group. These findings support earlier evidence that temporal processing is impaired in ASD.
4. Tian Y, Green PG, Stamova B, Hertz-Picciotto I, Pessah IN, Hansen R, Yang X, Gregg JP, Ashwood P, Jickling G, Van de Water J, Sharp FR. {{Correlations of Gene Expression with Blood Lead Levels in Children with Autism Compared to Typically Developing Controls}}. {Neurotox Res};2009 (Nov 17)
The objective of this study was to examine the correlation between gene expression and lead (Pb) levels in blood in children with autism (AU, n = 37) compared to typically developing controls (TD, n = 15). We postulated that, though lead levels did not differ between the groups, AU children might metabolize lead differently compared to TD children. RNA was isolated from blood and processed on Affymetrix microarrays. Separate analyses of covariance (ANCOVA) corrected for age and gender were performed for TD, AU, and all subjects (AU + TD). To reduce false positives, only genes that overlapped these three ANCOVAs were considered. Thus, 48 probe sets correlated with lead levels in both AU and TD subjects and were significantly different between the groups (p(Diagnosis x log(2) Pb) < 0.05). These genes were related mainly to immune and inflammatory processes, including MHC Class II family members and CD74. A large number (n = 791) of probe sets correlated (P </= 0.05) with lead levels in TD but not in AU subjects; and many probe sets (n = 162) correlated (P </= 0.05) with lead levels in AU but not in TD subjects. Only 30 probe sets correlated (P </= 0.05) with lead levels in a similar manner in the AU and TD groups. These data show that AU and TD children display different associations between transcript levels and low levels of lead. We postulate that this may relate to the underlying genetic differences between the two groups, though other explanations cannot be excluded.
5. Willemsen MH, Fernandez BA, Bacino CA, Gerkes E, de Brouwer AP, Pfundt R, Sikkema-Raddatz B, Scherer SW, Marshall CR, Potocki L, van Bokhoven H, Kleefstra T. {{Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome}}. {Eur J Hum Genet};2009 (Nov 18)
The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes.European Journal of Human Genetics advance online publication, 18 November 2009; doi:10.1038/ejhg.2009.192.
