1. Bremer A, Giacobini M, Eriksson M, Gustavsson P, Nordin V, Fernell E, Gillberg C, Nordgren A, Uppstromer A, Anderlid BM, Nordenskjold M, Schoumans J. {{Copy number variation characteristics in subpopulations of patients with autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Mar);156(2):115-124.
Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P = 0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs. (c) 2010 Wiley-Liss, Inc.
2. Chang SC, Pauls DL, Lange C, Sasanfar R, Santangelo SL. {{Common genetic variation in the GAD1 gene and the entire family of DLX homeobox genes and autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Mar);156(2):233-239.
Biological and positional evidence supports the involvement of the GAD1 and distal-less homeobox genes (DLXs) in the etiology of autism. We investigated 42 single nucleotide polymorphisms in these genes as risk factors for autism spectrum disorders (ASD) in a large family-based association study of 715 nuclear families. No single marker showed significant association after correction for multiple testing. A rare haplotype in the DLX1 promoter was associated with ASD (P-value = 0.001). Given the importance of rare variants to the etiology of autism revealed in recent studies, the observed rare haplotype may be relevant to future investigations. Our observations, when taken together with previous findings, suggest that common genetic variation in the GAD1 and DLX genes is unlikely to play a critical role in ASD susceptibility. (c) 2010 Wiley-Liss, Inc.
3. Crepel A, Steyaert J, De la Marche W, De Wolf V, Fryns JP, Noens I, Devriendt K, Peeters H. {{Narrowing the critical deletion region for autism spectrum disorders on 16p11.2}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Mar);156(2):243-245.
4. Kaluzna-Czaplinska J. {{Noninvasive urinary organic acids test to assess biochemical and nutritional individuality in autistic children}}. {Clin Biochem};2011 (Feb 4)
Objectives Quantitative organic acid testing can give information about potential problems, especially with energy production, neurotransmitter metabolism, intestinal dysbiosis and nutritional individuality which is very important in autistic children. The aim of this study was to find out potential differences between the levels of organic acids in the urine of autistic and non autistic children. Design and methods The organic acids in the urine were determined by capillary gas chromatography/mass spectrometry (GC/MS). All overnight urine samples were collected from 35 autistic children and 36 neurologically normal children as healthy controls (4-10years). RESULTS: Significant differences were found between the autistic children and the control group in organic acids: 2-oxoglutaric, isocitric, citric, 4-hydroxybenzoic, 4-hydroxyphenylacetic, hippuric, adipic, suberic (all with p<0.05). CONCLUSION: Organic acids test can be used to assess an individual need for nutrient and biochemical abnormalities, especially important for autistic children.
5. Khajuria R, Gupta N, Sapra S, Gulati S, Ghosh M, Kalra V, Kabra M. {{Novel non-identical MECP2 mutations in Rett syndrome family: A rare presentation}}. {Brain Dev};2011 (Feb 5)
INTRODUCTION: Rett syndrome (RS), an X-linked neurodevelopmental disorder and the common cause of mental retardation in females, is caused by methyl CpG binding protein 2 (MECP2) gene mutations with a frequency of more than 95% in classical Rett patients. Majority of RS cases are sporadic but few familial cases caused by either skewed X-chromosome inactivation in healthy female carriers or mosaicism in male carriers are also reported. Most of the times, the mutation carried in a family is the same as found in affected child. METHODS AND RESULTS: Here we report a unique family carrying non-identical MECP2 mutations in exon 2 wherein the proband with classical RS was carrying a de-novo early truncating frameshift mutation while her asymptomatic mother was carrying a missense mutation, both predicted as pathogenic mutations. CONCLUSIONS: These findings further validate the importance of MECP2 mutation screening in parents of all mutation positive patients and careful evaluation of the pathogenicity of the mutation found in asymptomatic carriers before providing genetic counseling to the family. The results also propose the role of other factors including other gene mutations, environmental and epigenetics factors in modifying the expression of MECP2 mutations.
6. Kistner-Griffin E, Brune CW, Davis LK, Sutcliffe JS, Cox NJ, Cook EH, Jr. {{Parent-of-origin effects of the serotonin transporter gene associated with autism}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Mar);156(2):139-144.
7. Murray MJ, Mayes SD, Smith LA. {{Brief Report: Excellent Agreement Between Two Brief Autism Scales (Checklist for Autism Spectrum Disorder and Social Responsiveness Scale) Completed Independently by Parents and the Autism Diagnostic Interview-Revised}}. {J Autism Dev Disord};2011 (Feb 8)
Agreement between the Autism Diagnostic Interview-Revised (ADI-R) and two brief scales completed by parents was 93.1% for the Checklist for Autism Spectrum Disorder (CASD) and 89.7% for the Social Responsiveness Scale (SRS) in a sample of adolescents with suspected autism spectrum disorders. Our study is consistent with others showing that brief scales like the CASD and SRS have strong psychometric support and compare favorably with the ADI-R. The CASD and SRS are each completed and scored in 15 min, whereas the ADI-R takes over 2 h to administer and score. The CASD and SRS offer a valid and cost effective alternative to lengthy and expensive measures and, by virtue of their brevity and simplicity, could facilitate diagnosis, access to treatment, and research.
8. Ratajczak HV. {{Theoretical aspects of autism: biomarkers?a review}}. {J Immunotoxicol};2011 (Jan-Mar);8(1):80-94.
Autism is dramatically increasing in incidence and is now considered an epidemic. There are no objective means to diagnose the disorder. Diagnosis is made subjectively, based on the perceived behavior of the subject. This review presents an approach toward development of an objective measure of autism. Covering the literature from 1943 to the present in the PubMed and Ovid Medline databases, this review summarizes evidence of hormones, metabolites, amino acids, and other biomarkers present in significantly different quantities in autistic subjects compared to age- and sex-matched controls. These differences can be measured in the gastrointestinal, immunologic, neurologic, and toxicologic systems of the body, with some biomarkers showing ubiquitous application. In addition, there are unifying concepts, i.e., increased vulnerability to oxidative stress, immune glutamatergic dysfunction, and pineal gland malfunction. The variances of the biomarkers from the norm present the opportunity to create biomarker arrays that when properly developed and analyzed could result in an objective diagnosis with a ranking of the severity of autism for each subject. The contribution of each biomarker to the overall diagnosis could be calculated, thus providing a profile pattern unique to the individual. This profile could consequently provide information for therapeutic interventions on an individual basis.
9. Ratajczak HV. {{Theoretical aspects of autism: Causes?A review}}. {J Immunotoxicol};2011 (Jan-Mar);8(1):68-79.
Autism, a member of the pervasive developmental disorders (PDDs), has been increasing dramatically since its description by Leo Kanner in 1943. First estimated to occur in 4 to 5 per 10,000 children, the incidence of autism is now 1 per 110 in the United States, and 1 per 64 in the United Kingdom, with similar incidences throughout the world. Searching information from 1943 to the present in PubMed and Ovid Medline databases, this review summarizes results that correlate the timing of changes in incidence with environmental changes. Autism could result from more than one cause, with different manifestations in different individuals that share common symptoms. Documented causes of autism include genetic mutations and/or deletions, viral infections, and encephalitis following vaccination. Therefore, autism is the result of genetic defects and/or inflammation of the brain. The inflammation could be caused by a defective placenta, immature blood-brain barrier, the immune response of the mother to infection while pregnant, a premature birth, encephalitis in the child after birth, or a toxic environment.
10. Shattuck PT, Wagner M, Narendorf S, Sterzing P, Hensley M. {{Post-high school service use among young adults with an autism spectrum disorder}}. {Arch Pediatr Adolesc Med};2011 (Feb);165(2):141-146.
OBJECTIVES: To produce nationally representative population estimates of rates of service use among young adults with an autism spectrum disorder during their first few years after leaving high school and to examine correlates of use. DESIGN: Nationally representative telephone survey from April 2007 to February 2008. SETTING: United States. PARTICIPANTS: Parents and guardians of young adults with autism spectrum disorders aged 19 to 23 years. Main Exposure Autism spectrum disorder. MAIN OUTCOME MEASURES: Use of the following services in the prior 2 years or since leaving high school: mental health services, medical evaluation and assessment, speech therapy, and case management. RESULTS: Rates of service use ranged from 9.1% for speech therapy to 41.9% for case management; 39.1% of youths with an autism spectrum disorder represented by the survey received no services. The adjusted odds of no services were higher among African American participants and those with low incomes. The adjusted odds of case management were lower among youths with high functional skills and those with low incomes. CONCLUSIONS: Rates of service disengagement are high after exiting high school. Disparities by race and socioeconomic status indicate a need for targeted outreach and services.
11. Zhu H, Sun Y, Zeng J, Sun H. {{Mirror neural training induced by virtual reality in brain-computer interfaces may provide a promising approach for the autism therapy}}. {Med Hypotheses};2011 (Feb 5)
Previous studies have suggested that the dysfunction of the human mirror neuron system (hMNS) plays an important role in the autism spectrum disorder (ASD). In this work, we propose a novel training program from our interdisciplinary research to improve mirror neuron functions of autistic individuals by using a BCI system with virtual reality technology. It is a promising approach for the autism to learn and develop social communications in a VR environment. A test method for this hypothesis is also provided.
