1. Abbes Z, Bouden A, Halayem S, Othman S, Bechir Halayem M. {{Clinical characteristics of Rett Syndrome}}. {Tunis Med};2011 (Oct);89(10):733-737.
Background: Rett Syndrome is a neurodevelopmental disorder, one of the least commonly occurring autism spectrum disorders (ASD),affecting mainly females. Aim: To describe features and molecular specificities of Rett syndrome. Methods: To identify articles for this review, a Pubmed search was conducted using the following keywords: Rett syndrome, regression,mutation, stereotypes. Results: This syndrome is characterized by cognitive impairment,communication dysfunction, stereotypic movement disorder, and growth failure. It is generally caused by mutations in the MECP2 gene. Rett Syndrome has a prevalence ranging from 10-20 000 females. Specific treatement is not available, but patients need a careful planning for long-term care, with multidisciplinary approaches.
2. Celestino-Soper PB, Shaw CA, Sanders SJ, Li J, Murtha MT, Ercan-Sencicek AG, Davis L, Thomson S, Gambin T, Chinault AC, Ou Z, German JR, Milosavljevic A, Sutcliffe JS, Cook EH, Jr., Stankiewicz P, State MW, Beaudet AL. {{Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE}}. {Hum Mol Genet};2011 (Nov 15);20(22):4360-4370.
Autism is a neurodevelopmental disorder with increasing evidence of heterogeneous genetic etiology including de novo and inherited copy number variants (CNVs). We performed array comparative genomic hybridization using a custom Agilent 1 M oligonucleotide array intended to cover 197 332 unique exons in RefSeq genes; 98% were covered by at least one probe and 95% were covered by three or more probes with the focus on detecting relatively small CNVs that would implicate a single protein-coding gene. The study group included 99 trios from the Simons Simplex Collection. The analysis identified and validated 55 potentially pathogenic CNVs, categorized as de novo autosomal heterozygous, inherited homozygous autosomal, complex autosomal and hemizygous deletions on the X chromosome of probands. Twenty percent (11 of 55) of these CNV calls were rare when compared with the Database of Genomic Variants. Thirty-six percent (20 of 55) of the CNVs were also detected in the same samples in an independent analysis using the 1 M Illumina single-nucleotide polymorphism array. Findings of note included a common and sometimes homozygous 61 bp exonic deletion in SLC38A10, three CNVs found in lymphoblast-derived DNA but not present in whole-blood derived DNA and, most importantly, in a male proband, an exonic deletion of the TMLHE (trimethyllysine hydroxylase epsilon) that encodes the first enzyme in the biosynthesis of carnitine. Data for CNVs present in lymphoblasts but absent in fresh blood DNA suggest that these represent clonal outgrowth of individual B cells with pre-existing somatic mutations rather than artifacts arising in cell culture. GEO accession number GSE23765 (http://www.ncbi.nlm.nih.gov/geo/, date last accessed on 30 August 2011). Genboree accession: http://genboree.org/java-bin/gbrowser.jsp?refSeqId=1868&entryPointId=chr17&from=5 3496072&to=53694382&isPublic=yes, date last accessed on 30 August 2011.
Lien vers le texte intégral (Open Access ou abonnement)
3. Coffee RL, Jr., Williamson AJ, Adkins CM, Gray MC, Page TL, Broadie K. {{In Vivo Neuronal Function of the Fragile X Mental Retardation Protein is Regulated by Phosphorylation}}. {Hum Mol Genet};2011 (Nov 11)
Fragile X syndrome (FXS), caused by loss of the Fragile X Mental Retardation 1 (FMR1) gene product (FMRP), is the most common heritable cause of intellectual disability and autism spectrum disorders. It has been long hypothesized that the phosphorylation of serine 500 (S500) in human FMRP controls its function as an RNA-binding translational repressor. To test this hypothesis in vivo, we employed neuronally targeted expression of three human FMR1 transgenes, including wildtype (hFMR1), dephosphomimetic (S500A-hFMR1) and phosphomimetic (S500D-hFMR1), in the Drosophila FXS disease model to investigate phosphorylation requirements. At the molecular level, dfmr1 null mutants exhibit elevated brain protein levels due to loss of translational repressor activity. This defect is rescued for an individual target protein and across the population of brain proteins by the phosphomimetic, whereas the dephosphomimetic phenocopies the null condition. At the cellular level, dfmr1 null synapse architecture exhibits increased area, branching and bouton number. The phosphomimetic fully rescues these synaptogenesis defects, whereas the dephosphomimetic provides no rescue. The presence of Futsch-positive (microtubule-associated MAP1B protein) supernumerary microtubule loops is elevated in dfmr1 null synapses. The human phosphomimetic restores normal Futsch loops, whereas the dephosphomimetic provides no activity. At the behavioral level, dfmr1 null mutants exhibit strongly impaired olfactory associative learning. The human phosphomimetic targeted only to the brain-learning center restores normal learning ability, whereas the dephosphomimetic provides absolutely no rescue. We conclude that human FMRP S500 phosphorylation is necessary for its in vivo function as a neuronal translational repressor and regulator of synaptic architecture, and for the manifestation of FMRP-dependent learning behavior.
Lien vers le texte intégral (Open Access ou abonnement)
4. Ekinci O, Arman AR, Melek I, Bez Y, Berkem M. {{The phenomenology of autistic regression: subtypes and associated factors}}. {Eur Child Adolesc Psychiatry};2011 (Nov 12)
This study aimed to investigate the association of autistic regression (AR) and subtypes of AR with medical, developmental and psychiatric factors. Fifty-seven children with autistic spectrum disorders (ASD) were included in the study. Two types of AR are defined as regression after a normal social/language development (type 1) and regression as the worsening of previously reported autistic features (type 2). The frequency of history of AR was 56.1%. Male gender and sleep problems were found to be associated with a positive history of AR. The frequency of gastrointestinal complaints/diseases was higher in children with regression type 2 when compared to the children with regression type 1. Future studies with larger sample size and prospective design will contribute to clarifying the phenomenology and the associated factors of AR.
Lien vers le texte intégral (Open Access ou abonnement)
5. Farzin F, Rivera SM, Whitney D. {{Resolution of spatial and temporal visual attention in infants with fragile X syndrome}}. {Brain};2011 (Nov);134(Pt 11):3355-3368.
Fragile X syndrome is the most common cause of inherited intellectual impairment and the most common single-gene cause of autism. Individuals with fragile X syndrome present with a neurobehavioural phenotype that includes selective deficits in spatiotemporal visual perception associated with neural processing in frontal-parietal networks of the brain. The goal of the current study was to examine whether reduced resolution of spatial and/or temporal visual attention may underlie perceptual deficits related to fragile X syndrome. Eye tracking was used to psychophysically measure the limits of spatial and temporal attention in infants with fragile X syndrome and age-matched neurotypically developing infants. Results from these experiments revealed that infants with fragile X syndrome experience drastically reduced resolution of temporal attention in a genetic dose-sensitive manner, but have a spatial resolution of attention that is not impaired. Coarse temporal attention could have significant knock-on effects for the development of perceptual, cognitive and motor abilities in individuals with the disorder.
Lien vers le texte intégral (Open Access ou abonnement)
6. Ghoneim OM, Ibrahim DA, El-Deeb IM, Lee SH, Booth RG. {{A novel potential therapeutic avenue for autism: Design, synthesis and pharmacophore generation of SSRIs with dual action}}. {Bioorg Med Chem Lett};2011 (Nov 15);21(22):6714-6723.
Autism symptoms are currently modulated by Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs slow onset of action limits their efficiency. The established synergistic activity of SSRIs and 5HT(1B/1D) autoreceptors antagonists motivated us to incorporate SSRIs and 5HT(1B/1D) antagonists in one ‘hybrid’ molecule. A library of virtual ‘hybrid’ molecules was designed using the tethering technique. A pharmacophore model was generated derived from 16 structurally diverse SSRIs (K(i)=0.013-5000nM) and used as 3D query. Compounds with fit values (2) were chosen for synthesis and subsequent in vitro biological evaluation. Our pharmacophore model is a promising milestone to a class of SSRIs with dual action.
Lien vers le texte intégral (Open Access ou abonnement)
7. Gray KM, Taffe J, Sweeney DJ, Forster S, Tonge BJ. {{Could head circumference be used to screen for autism in young males with developmental delay?}}. {J Paediatr Child Health};2011 (Nov 14)
Aim: Research has suggested an abnormal acceleration in head circumference growth in children with autism within the first 12 months of life. This study aimed to examine head circumference at birth and head circumference growth rates in young children with autism and developmental delay, and young children with developmental delay without autism. Methods: This study assessed head circumference at birth and rate of change in head circumference in young children with autism (n= 86) and children with developmental delay without autism (n= 40). Results: For both groups of children, head circumference at birth and head circumference growth were compared with Centers for Disease Control normative data. No differences were found between the group of children with autism and developmental delay compared with the group with developmental delay only. However, when the sample was compared with a range of selected Centers for Disease Control normative medians, the children with autism were found to have significantly smaller head circumferences at birth and significantly larger head circumference at 18.5 months of age. Conclusions: These results are discussed in relation to the potential of accelerated head circumference growth as an early marker for autism. This study failed to find a difference in the head circumferences of children with autism and developmental delay and children with developmental delay only, thus suggesting that head circumference measurement has limited value as an early marker for autism.
Lien vers le texte intégral (Open Access ou abonnement)
8. Gupta VB, Lauffer D. {{Should the Diagnosis of Autism be Made Only on the Basis of a Standardized Test?}}. {J Dev Behav Pediatr};2011 (Nov 9)
This commentary argues that a standardized tool such as Autism Diagnostic Observation Schedule (ADOS) is not always required to make the diagnosis of autism, which can be made by obtaining a thorough history and performing an astute clinical examination as William Osler, founder of John Hopkins School of Medicine taught or Dr. Leo Kanner practiced.
Lien vers le texte intégral (Open Access ou abonnement)
9. Kaluzna-Czaplinska J, Blaszczyk S. {{The level of arabinitol in autistic children after probiotic therapy}}. {Nutrition};2011 (Nov 11)
OBJECTIVE: The level of D-arabinitol (DA) and the ratio of D-/L-arabinitol (DA/LA) in the urine of children with autism were investigated. The changes in DA/LA after probiotic treatment in urine samples of children with autism were studied. METHODS: DA and LA and the DA/LA ratio were identified by capillary gas chromatography/mass spectrometry in urine before and after the probiotic therapy. RESULTS: The level of DA is significantly higher (P < 0.05) in the urine of autistic children before (A) and after probiotic supplementation (A1) (160.04 +/- 22.88 mumol/mmol creatinine and 89.53 +/- 37.41 mumol/mmol creatinine, respectively). Nonetheless, the probiotic supplementation let to a significant decrease in DA and DA/LA and to a significant improvement in ability of concentration and carrying out orders. CONCLUSION: The use of probiotics seems to be helpful in reducing the level of DA and the ratio of DA/LA in the urine of children with autism.
Lien vers le texte intégral (Open Access ou abonnement)
10. Levine TP, Sheinkopf SJ, Pescosolido M, Rodino A, Elia G, Lester B. {{Physiologic Arousal to Social Stress in Children with Autism Spectrum Disorders: A Pilot Study}}. {Res Autism Spectr Disord};2012 (Winter);6(1):177-183.
Little is known about arousal to socially stressful situations in children with Autism Spectrum Disorders. This preliminary study investigates physiologic arousal in children with high functioning autism (HFA, n=19) compared to a comparison group (n=11) before, during, and after the Trier Social Stress Test. The HFA group was more likely to have a decrease in salivary cortisol following the stressor, while the comparison group was more likely to have an increase (p=.02). However, there was no difference in electrodermal activity, a measure of sympathetic arousal, or vagal tone, a measure of parasympathetic activity, between groups. These findings implicate a differential neuroendocrine response to social stress in children with HFA despite similar sympathetic and parasympathetic responses during a stressor. Further studies are required to substantiate this finding.
Lien vers le texte intégral (Open Access ou abonnement)
11. Li N, Chen G, Song X, Du W, Zheng X. {{Prevalence of autism-caused disability among Chinese children: A national population-based survey}}. {Epilepsy Behav};2011 (Nov 11)
Few articles in English have discussed the prevalence of autism in China. The work described here was aimed at estimating the prevalence rate of autism-caused disability among Chinese children and exploring family environmental factors associated with autism based on a national population sample. Data for this study were derived from the Second China National Sample Survey on Disability. A weighted number of 77,301 disabled children affected by autism were identified, yielding a prevalence rate of 2.38/10,000. A history of mental disorders in adults was strongly associated with autism. The prevalence of autism in Chinese children was underestimated, and the lack of qualified professionals able to identify and diagnose autism was the main reason. Countermeasures are warranted to obtain a more precise overview of autism in China.
Lien vers le texte intégral (Open Access ou abonnement)
12. Shamberger RJ. {{Autism Rates Associated with Nutrition and the WIC Program}}. {J Am Coll Nutr};2011 (Oct);30(5):348-353.
OBJECTIVES: Autism rates in the United States are increasing at a rate of 15% per year. Autistic children are diagnosed by age 3 when they have problems communicating and interacting socially. This study uses nutritional epidemiology and an ecologic study design to link the possible cause of autism to nutrition by creating autism rates for the 50 states of America and comparing them with published measures of infant nutrition such as duration of exclusive breast-feeding and participation in the Women, Infants, and Children (WIC) program. The percentage of infants with measles, mumps, and rubella (MMR) inoculations was also compared with the autism rates. Study DESIGN: Autism rates for each state were established. The percentage of infants who participate in the WIC program for low-income families was calculated for each of the 50 states as well as 21 New Jersey and 30 Oregon counties and compared with their autism rates. An ecologic study design with correlation coefficients is limited, but it is useful for generating hypotheses to be tested. RESULTS: The states with the highest WIC participation have significantly lower autism rates (p < 0.02). A similar pattern was observed in 21 New Jersey counties (p < 0.02) and 30 Oregon counties (p < 0.05). In contrast, there was a direct correlation with the increasing percentage of women exclusively breast-feeding from 2000-2004 (p < 0.001). Infants who were solely breast-fed had diets that contained less thiamine, riboflavin, and vitamin D than the minimal daily requirements (MDR). There was no correlation of MMR inoculations with the autism rate. CONCLUSION: The mothers who are exclusively breast-feeding should also continue their prenatal vitamins or their equivalent and make better dietary choices. These results suggest that autism may be nutritionally related to a possible deficiency of riboflavin or the cognitive vitamins such as thiamine or vitamin D. However, due to an ecologic study design there is a potential for fallacy because individuals were not examined. The results suggest the need for a robust observational study in advance of, and to confirm the need for, an intervention study.
Lien vers le texte intégral (Open Access ou abonnement)
13. Yasui DH, Scoles HA, Horike S, Meguro-Horike M, Dunaway KW, Schroeder DI, Lasalle JM. {{15q11.2-13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain}}. {Hum Mol Genet};2011 (Nov 15);20(22):4311-4323.
Copy number variations (CNVs) within human 15q11.2-13.3 show reduced penetrance and variable expressivity in a range of neurologic disorders. Therefore, characterizing 15q11.2-13.3 chromatin structure is important for understanding the regulation of this locus during normal neuronal development. Deletion of the Prader-Willi imprinting center (PWS-IC) within 15q11.2-13.3 disrupts long-range imprinted gene expression resulting in Prader-Willi syndrome. Previous results establish that MeCP2 binds to the PWS-IC and is required for optimal expression of distal GABRB3 and UBE3A. To examine the hypothesis that MeCP2 facilitates 15q11.2-13.3 transcription by linking the PWS-IC with distant elements, chromosome capture conformation on chip (4C) analysis was performed in human SH-SY5Y neuroblastoma cells. SH-SY5Y neurons had 2.84-fold fewer 15q11.2-13.3 PWS-IC chromatin interactions than undifferentiated SH-SY5Y neuroblasts, revealing developmental chromatin de-condensation of the locus. Out of 68 PWS-IC interactions with15q11.2-13.3 identified by 4C analysis and 62 15q11.2-13.3 MeCP2-binding sites identified by previous ChIP-chip studies, only five sites showed overlap. Remarkably, two of these overlapping PWS-IC- and MeCP2-bound sites mapped to sites flanking CHRNA7 (cholinergic receptor nicotinic alpha 7) encoding the cholinergic receptor, nicotinic, alpha 7. PWS-IC interaction with CHRNA7 in neurons was independently confirmed by fluorescent in situ hybridization analysis. Subsequent quantitative transcriptional analyses of frontal cortex from Rett syndrome and autism patients revealed significantly reduced CHRNA7 expression compared with controls. Together, these results suggest that transcription of CHRNA7 is modulated by chromatin interactions with the PWS-IC. Thus, loss of long-range chromatin interactions within 15q11.2-13.3 may contribute to multiple human neurodevelopmental disorders.
