1. Al-Yafee YA, Al-Ayadhi LY, Haq SH, El-Ansary AK. {{Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia}}. {BMC Neurol};2011 (Nov 4);11(1):139.
ABSTRACT: BACKGROUND: Xenobiotics are neurotoxins that dramatically alter the health of the child. In addition, an inefficient detoxification system leads to oxidative stress, gut dysbiosis, and immune dysfunction. The consensus among physicians who treat autism with a biomedical approach is that those on the spectrum are burdened with oxidative stress and immune problems. In a trial to understand the role of detoxification in the etiology of autism, selected parameters related to sulfur-dependent detoxification mechanisms in plasma of autistic children from Saudi Arabia will be investigated compared to control subjects. METHODS: 20 males autistic children aged 3-15 years and 20 age and gender matching healthy children as control group were included in this study. Levels of reduced glutathione (GSH), total (GSH+GSSG), glutathione status (GSH/ GSSG), glutathione reductase (GR), glutathione- s-transferase (GST), thioredoxin (Trx), thioredoxin reductase (TrxR) and peroxidoxins (Prxs I and III) were determined. RESULTS: Reduced glutathione, total glutathione, GSH/GSSG and activity levels of GST were significantly lower, GR shows non-significant differences, while, Trx, TrxR and both Prx I and III recorded a remarkably higher values in autistics compared to control subjects. CONCLUSION: The impaired glutathione status together with the elevated Trx and TrxR and the remarkable over expression of both Prx I and Prx III, could be used as diagnostic biomarkers of autism.
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2. Chung RH, Ma D, Wang K, Hedges DJ, Jaworski JM, Gilbert JR, Cuccaro ML, Wright HH, Abramson RK, Konidari I, Whitehead PL, Schellenberg GD, Hakonarson H, Haines JL, Pericak-Vance MA, Martin ER. {{An X-chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males}}. {Mol Autism};2011 (Nov 4);2(1):18.
ABSTRACT: BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males compared to females and evidence of suggestive linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes for ASD. METHODS: We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS datasets: two family datasets and one case-control dataset. We performed meta- and joint analyses on the combined family and case-control datasets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family datasets as a discovery dataset and the case-control dataset as a validation dataset. RESULTS: One SNP rs17321050 in the TBL1X (transducin (beta)-like 1X-linked, OMIM: 300196) gene showed chromosome-wide significance in the meta-analysis (p-value=4.86x10E-6) and joint analysis (p-value=4.53x10E-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery dataset (p=5.89x10E-3) and passed the replication threshold in the validation (p=2.56x10E-4) dataset. Two other SNPs in the same gene in LD linkage disequilibrium (LD) with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis. CONCLUSIONS: TBL1X is in the Wnt signaling pathway, which has previously been implicated in autism. Deletions in the Xp22.2-Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, through both meta- and joint and replication analyses, suggest that TBL1X may play a role in ASD risk.
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3. Finestack LH, Palmer M, Abbeduto L. {{Macrostructural Narrative Language of Adolescents and Young Adults with Down Syndrome or Fragile X Syndrome}}. {Am J Speech Lang Pathol};2011 (Nov 2)
PURPOSE: To gain a better understanding of language abilities, the expressive macrostructural narrative language abilities of verbally expressive adolescents and young adults with Down syndrome (DS) and those with fragile X syndrome (FXS) were examined. METHOD: The authors evaluated 24 adolescents and young adults with DS, 12 male adolescents and young adults with FXS, and 21 younger children with typical development (TD). Narrative samples were assessed at the macrostructural level using the Narrative Scoring Scheme (NSS; Heilmann, Miller, Nockerts, & Dunaway, 2010). Three group comparisons were made using: (a) the full sample matched on nonverbal mental age, (b) a subset of the participants individually matched on nonverbal mental age, and (c) a subset of participants individually matched on mean length of utterance. RESULTS: Study analyses revealed that the DS and FXS groups significantly outperformed the TD group on a limited number of NSS measures. No significant differences emerged between the DS and FXS groups. CONCLUSIONS: Study results suggest that some aspects of macrostructural narrative language may be relative strengths for adolescents and young adults with DS and those with FXS. These results can be used to create a more nuanced and informed approach to assessment and intervention for these populations.
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4. Gebril OH, Meguid NA. {{HFE gene polymorphisms and the risk for autism in Egyptian children and impact on the effect of oxidative stress}}. {Dis Markers};2011 (Jan 1);31(5):289-294.
Background: Autism is among the commonest neurodevelopmental childhood disorders worldwide; its aetiology is still unknown. Iron metabolism alteration in the central nervous system is recently implicated as a risk factor for several neurodegenerative disorders. Haemochromatosis HFE gene polymorphisms (p.H63D and p.C282Y) have shown significant association with several neurological diseases. Some evidences show altered iron related proteins in serum of autistic children. The aim of this work is to conduct a preliminary pilot study for the association of HFE polymorphisms and autism.Methods: All cases were referred from the clinic of special needs, National Research Centre, Cairo. Clinical diagnosis was based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Whole genome DNA was extracted; p.H63D and p.C282Y genotyping was studied using specific sequence amplification followed by restriction enzyme digestion on a sample of autism patients (25 cases) and twenty controls. Results: The p.H63D is more abundant than the C282Y among both autism and control samples. No significant association of p.H63D nor p.C282Y polymorphism and autism was revealed. Conclusion: We here report on the first pilot study of the possible genetic association between autism and HFE gene polymorphisms among Egyptians. Although our results do not prove the role of HFE polymorphisms as risk factors for autism, yet this does not exclude the role of iron in this prevalent disorder. Further extended studies are recommended to include other iron metabolism genes.
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5. Guo W, Murthy AC, Zhang L, Johnson EB, Schaller EG, Allan AM, Zhao X. {{Inhibition of GSK3beta improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome}}. {Hum Mol Genet};2011 (Nov 2)
Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis and hippocampus-dependent learning and FMRP regulates adult neural stem cell fate through translational regulation of GSK3beta, we investigated the effects of a GSK3beta inhibitor, SB216763, on FMRP mutant mice (Fmr1 KO). We found that inhibition of GSK3beta could reverse the hippocampus-dependent learning deficits and rescue adult hippocampal neurogenesis at multiple stages in Fmr1 KO mice. Our results point to GSK3beta inhibition as a potential treatment for the learning deficits seen in FXS.
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6. Hong S, Ke X, Tang T, Hang Y, Chu K, Huang H, Ruan Z, Lu Z, Tao G, Liu Y. {{Detecting abnormalities of corpus callosum connectivity in autism using magnetic resonance imaging and diffusion tensor tractography}}. {Psychiatry Res};2011 (Oct 31)
The corpus callosum (CC) has emerged as one of the primary targets of autism research. To detect aberrant CC interhemispheric connectivity in autism, we performed T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)-based tractography in 18 children with high functioning autism (HFA) and 16 well-matched typically developing (TD) children. We compared global and regional T1 measures (CC volume, and CC density), and the DTI measures [fractional anisotropy (FA), apparent diffusion coefficient (ADC), average fiber length (AFL), and fiber number (FN)] of transcallosal fibers, between the two groups. We also evaluated the relationships between scores on the Childhood Autism Rating Scale (CARS) and CC T1 or DTI measurements. Significantly less white matter density in the anterior third of the CC, and higher ADC and lower FN values of the anterior third transcallosal fiber tracts were found in HFA patients compared to TD children. These results suggested that the anterior third CC density and transcallosal fiber connectivity were affected in HFA children.
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7. Malenfant P, Liu X, Hudson ML, Qiao Y, Hrynchak M, Riendeau N, Hildebrand MJ, Cohen IL, Chudley AE, Forster-Gibson C, Mickelson EC, Rajcan-Separovic E, Lewis ME, Holden JJ. {{Association of GTF2i in the Williams-Beuren Syndrome Critical Region with Autism Spectrum Disorders}}. {J Autism Dev Disord};2011 (Nov 3)
Duplications of 7q11.23, deleted in Williams-Beuren Syndrome, have been implicated in autism spectrum disorders (ASDs). A 1.5 Mb duplication was identified in one girl with severe expressive language deficits and anxiety among 1,142 ASD individuals screened for this duplication. Family-based association studies of Tag-SNPs in three genes (STX1A , CYLN2 and GTF2i) in two multiplex autism family cohorts revealed strong association of two GTF2i SNPs and their haplotype in Cohort 1 and the combined families. The risk alleles and haplotype were associated with severe problems in social interaction and excessive repetitive behaviors. Our findings suggest the GTF2i gene is important in the etiology of autism in individuals with this duplication and in non-duplication cases with severe social interaction problems and repetitive behaviors.
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8. Menezo Y, Mares P, Cohen M, Brack M, Viville S, Elder K. {{Autism, imprinting and epigenetic disorders: a metabolic syndrome linked to anomalies in homocysteine recycling starting in early life??}}. {J Assist Reprod Genet};2011 (Nov 3)
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9. Nygren G, Cederlund M, Sandberg E, Gillstedt F, Arvidsson T, Carina Gillberg I, Westman Andersson G, Gillberg C. {{The Prevalence of Autism Spectrum Disorders in Toddlers: A Population Study of 2-Year-Old Swedish Children}}. {J Autism Dev Disord};2011 (Nov 3)
Autism Spectrum Disorder (ASD) is more common than previously believed. ASD is increasingly diagnosed at very young ages. We report estimated ASD prevalence rates from a population study of 2-year-old children conducted in 2010 in Gothenburg, Sweden. Screening for ASD had been introduced at all child health centers at child age 21/2 years. All children with suspected ASD were referred for evaluation to one center, serving the whole city of Gothenburg. The prevalence for all 2-year-olds referred in 2010 and diagnosed with ASD was 0.80%. Corresponding rates for 2-year-olds referred to the center in 2000 and 2005 (when no population screening occurred) were 0.18 and 0.04%. Results suggest that early screening contributes to a large increase in diagnosed ASD cases.
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10. Verhoeven JS, Rommel N, Prodi E, Leemans A, Zink I, Vandewalle E, Noens I, Wagemans J, Steyaert J, Boets B, Van de Winckel A, De Cock P, Lagae L, Sunaert S. {{Is There a Common Neuroanatomical Substrate of Language Deficit between Autism Spectrum Disorder and Specific Language Impairment?}}. {Cereb Cortex};2011 (Nov 2)
Discussion of an overlap between specific language impairment (SLI) and autism spectrum disorder (ASD) is on going. The most intriguing overlap between both phenotypes is the similarity in the observed language deficits described in SLI and a subgroup of ASD with co-occurring linguistic impairment, ASD-LI. Examining whether a similar neuroanatomical substrate underlies this phenotypical linguistic overlap, we studied the white matter microstructural properties of the superior longitudinal fascicle (SLF) of 19 ASD-LI adolescents (mean age 13.8 +/- 1.6 years) and 21 age-matched controls and compared them with 13 SLI children (mean age 10.1 +/- 0.4 years) and 12 age-matched controls. A linguistic profile assessment and a diffusion tensor imaging analysis of the SLF were performed. Linguistic testing revealed a mixed receptive-expressive disorder profile in both groups, confirming their overlap at phenotypical level. At neuroanatomical level, no significant differences in mean SLF fractional anisotropy (FA) and mean SLF apparent diffusion coefficient values between ASD-LI participants and controls were seen. By contrast, the mean SLF FA was significantly reduced in the SLI children as compared with their controls. The observation of structural SLF disturbances in SLI but not in ASD-LI suggests the existence of a different neuroanatomical substrate for the language deficits in both disorders.
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11. Wilson NJ. {{Book Review Editor: Rachel Mayes B. Marks , J. Sisarak , & T. Heller (Eds.). Health Matters for People with Developmental Disabilities: Creating a Sustainable Health Promotion Program . Baltimore, MD : Brookes . 2010 . 152 pp. US $29.95 . ISBN 978-1-59857-000-7}}. {J Intellect Dev Disabil};2011 (Nov 4)
