1. Cardoza B, Clarke A, Wilcox J, Gibbon F, Smith PE, Archer H, Hryniewiecka-Jaworska A, Kerr M. {{Epilepsy in Rett syndrome: Association between phenotype and genotype, and implications for practice}}. {Seizure};2011 (Jul 15)
PURPOSE: To investigate the association between genotype (methyl-CpG-binding protein 2 (MECP2 gene mutation)) and epileptic seizure phenotype in Rett syndrome. METHODS: We used the British Isles Rett syndrome survey to identify 137 subjects with one of the nine most frequent MECP2 gene mutations and invited their parents or carers to participate in a postal questionnaire and telephone interview. The questionnaire recorded information about epileptic seizure types, non-epileptic vacant spells and treatments. Two investigators conducted telephone interviews and three epileptologists classified their epileptic seizures. RESULTS: 89 subjects (65%) responded. The epilepsy prevalence was 67%, and 74% had non-epileptic vacant spells. The epilepsy prevalence within specific genotypes ranged from 47% (mutation C-terminal deletion, downstream of the Transcription Repression Domain) to 100% (mutation p.R270X, c.808C>T). The prevalence of non-epileptic vacant spells within genotypes ranged from 50% (mutation p.R306C, c.916C>T) to 100% (mutation p.R106W, c.316C>T). The epileptologists differed considerably in their classification of events, particularly of non-epileptic vacant spells. CONCLUSIONS: The large majority of people with Rett syndrome have epilepsy. Most have multiple epileptic seizure types, although generalised tonic-clonic seizures are the most common. There were no significant clinical differences between genotypes. The clinical differentiation of non-epileptic vacant spells is difficult. Discordance in epileptic seizure classification between clinicians suggests that caution is needed, since the clinical history alone cannot adequately classify the epileptic seizure type in Rett syndrome.
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2. Curran S, Dworzynski K, Happe F, Ronald A, Allison C, Baron-Cohen S, Brayne C, Bolton PF. {{No major effect of twinning on autistic traits}}. {Autism Res};2011 (Jul 15)
Background: It has been questioned whether the process of twinning might be a risk factor for autism spectrum conditions (ASC) and autistic traits. Aim: We sought to determine whether autistic traits and probable disorder, as measured by the Childhood Autism Spectrum Test (CAST), were more pronounced in twins compared to singletons. Samples: Data were analyzed from two large population-based samples of UK children, twins (n = 5,142 twin pairs, aged 8 years) and singletons (n = 2,805, aged 5-9 years). Results: Distributions of CAST scores in both groups were negatively skewed and scores for twins were more variable than singletons. Mean CAST total scores and standard errors (SE) were not significantly different for twins (5.1; SE 0.04) compared to singletons (4.9; SE 0.08). Moreover, contrary to expectations, the likelihood of scoring above the threshold for possible ASC was significantly lower in the twins than the singletons (OR = 0.69; P = 0.002). Subsidiary analyses of CAST scores according to sex, twin type, and subscale scores representing the subdomains of autism found a few significant differences (P<0.01), but the effect sizes for these differences were small and none exceeded eta(2) = 0.005. The explanation for these small differences remains obscure, but the very small effect sizes mean they are of little importance. Conclusions: Our results do not provide evidence to support twinning as a risk factor in the development of autistic traits. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
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3. El-Ansary AK, Bacha AB, Ayahdi LY. {{Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia}}. {Clin Biochem};2011 (Jul 6)
OBJECTIVE: This study aims to clarify the relationship between blood Pb(2+) concentration as a ubiquitous environmental pollutant and plasma neurotransmitters as biochemical parameters that reflect brain function in Saudi autistic patients. METHODS: RBC’s lead content together with plasma concentration of gamma aminobutyric acid (GABA), serotonin (5HT) and dopamine (DA) were measured in 25 Saudi autistic patients and compared to 16 age-matching control samples. RESULTS: The obtained data recorded that Saudi autistic patients have a remarkable higher levels of Pb(2+) and significantly elevated levels of GABA, 5HT and DA compared to healthy subjects. ROC analysis revealed satisfactory values of specificity and sensitivity of the measured parameters. CONCLUSION: This study suggests that postnatal lead toxicity in autistic patients of Saudi Arabia could represent a causative factor in the pathogenesis of autism. Elevated GABA, 5HT and DA were discussed in relation to the chronic lead toxicity recorded in the investigated autistic samples.
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4. Kumar A, Fang P, Park H, Guo M, Nettles KW, Disney MD. {{A Crystal Structure of a Model of the Repeating r(CGG) Transcript Found in Fragile X Syndrome}}. {Chembiochem};2011 (Jul 15)
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5. Neumann N, Dubischar-Krivec AM, Poustka F, Birbaumer N, Bolte S, Braun C. {{Electromagnetic evidence of altered visual processing in autism}}. {Neuropsychologia};2011 (Jul 6)
Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli and enhanced activity of early visual areas. Ten autistic and ten matched control participants underwent 151-channel whole-head magnetoencephalography. Participants were presented with 400 embedded or isolated letters (‘S’ or ‘H’) and asked to indicate which of the two letters was shown. Performance was equal in both groups, but event-related magnetic fields differed between groups in an early (100-150ms) and a later (350-400ms) time window. In the early time window, autistic individuals differed from control participants in the embedded, but not in the isolated condition, reflecting reduced processing of the irrelevant context in autistic individuals. In the later time window, amplitude differences between the embedded and isolated conditions were measured in control participants only, suggesting that « disembedding » processes were not required in autistic individuals. Source localisation indicated that activity in individuals with ASD peaked in the primary visual cortex in both conditions and time windows indicating an effortless (automatic, bottom-up) local process, whereas activity in controls peaked outside the visual cortex.
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6. Pizzarelli R, Cherubini E. {{Alterations of GABAergic signaling in autism spectrum disorders}}. {Neural Plast};2011;2011:297153.
Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Interestingly, in a small number of cases, ASDs are associated with single mutations in genes encoding for neuroligin-neurexin families. These are adhesion molecules which, by regulating transsynaptic signaling, contribute to maintain a proper excitatory/inhibitory (E/I) balance at the network level. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, at late embryonic/early postnatal stages has been shown to depolarize and excite targeted cell through an outwardly directed flux of chloride. The depolarizing action of GABA and associated calcium influx regulate a variety of developmental processes from cell migration and differentiation to synapse formation. Here, we summarize recent data concerning the functional role of GABA in building up and refining neuronal circuits early in development and the molecular mechanisms regulating the E/I balance. A dysfunction of the GABAergic signaling early in development leads to a severe E/I unbalance in neuronal circuits, a condition that may account for some of the behavioral deficits observed in ASD patients.
