1. Armani R, Archer H, Clarke A, Vasudevan P, Zweier C, Ho G, Williamson S, Cloosterman D, Yang N, Christodoulou J. {{Transcription Factor 4 and Myocyte Enhancer Factor 2C mutations are not common causes of Rett syndrome}}. {Am J Med Genet A};2012 (Mar 1)
The systematic screening of Rett syndrome (RTT) patients for pathogenetic sequence variations has focused on three genes that have been associated with RTT or related clinical phenotypes, namely MECP2, CDKL5, and FOXG1. More recently, it has been suggested that phenotypes associated with TCF4 and MEF2C mutations may represent a form of RTT. Here we report on the screening of the TCF4 and MEF2C genes in a cohort of 81 classical, atypical, and incomplete atypical RTT patients harboring no known mutations in MECP2, CDKL5, and FOXG1 genes. No pathogenetic sequence variations were identified in the MEF2C gene in our cohort. However, a frameshift mutation in TCF4 was identified in a patient with a clinical diagnosis of « variant » RTT, in whom the clinical evolution later raised the possibility of Pitt-Hopkins syndrome. Although our results suggest that these genes are not commonly associated with RTT, we note the clinical similarity between RTT and Pitt-Hopkins syndrome, and suggest that RTT patients with no mutation identified in MECP2 be considered for molecular screening of the TCF4 gene. (c) 2012 Wiley Periodicals, Inc.
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2. Berg AT, Plioplys S. {{Epilepsy and autism: Is there a special relationship?}}. {Epilepsy Behav};2012 (Feb 28)
Increasingly, there has been an interest in the association between epilepsy and autism. The high frequency of autism in some of the early-onset developmental encephalopathic epilepsies is frequently cited as evidence of the relationship between autism and epilepsy. While these specific forms of epilepsy carry a higher-than-expected risk of autism, most, if not all, of the association may be due to intellectual disability (ID). The high prevalence of interictal EEG discharges in children with autism is also cited as further evidence although errors in the diagnosis of epilepsy seem to account for at least part of those findings. The prevalence of ID is substantially elevated in children with either epilepsy or autism. In the absence of ID, there is little evidence of a substantial, if any, increased risk of autism in children with epilepsy. Further, although the reported prevalence of autism has increased over the last several years, much of this increase may be attributable to changes in diagnostic practices, conceptualization of autism in the presence of ID, and laws requiring provision of services for children with autism. In the context of these temporal trends, any further efforts to tease apart the relationships between epilepsy, ID, and autism will have to address head-on the accuracy of diagnosis of all three conditions before we can determine whether there is, indeed, a special relationship between autism and epilepsy.
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3. Cottenceau H, Roux S, Blanc R, Lenoir P, Bonnet-Brilhault F, Barthelemy C. {{Quality of life of adolescents with autism spectrum disorders: comparison to adolescents with diabetes}}. {Eur Child Adolesc Psychiatry};2012 (Mar 1)
Relationships are of great importance during adolescence. Because of their social, communication and behavioral impairments, adolescents with Asperger’s syndrome (AS) or high functioning autism (HFA) probably suffer from considerable impairment of their quality of life when facing their peers in school. Nevertheless, only one recent study has been published on this subject, indicating a lower health-related quality of life in children and adolescents with autism spectrum disorders (ASD) than in healthy controls. The goals of our study were to clarify the consequences of autistic disorder without mental retardation on such adolescents’ daily lives, and to consider them in comparison with the impact of a chronic somatic disease (diabetes) and with the period of adolescence itself, using the VSP-A questionnaire. Adolescents with diabetes were chosen as a comparison group because of the encumbrance of having a constant need for insulin supplementation, to be assimilated to the constant need for communicative adjustments in teenagers with ASD, and the consequences in daily life. The effects of social skill training and social support on quality of life and the appropriateness of using the VSP-A in this population were also studied. Twenty-six adolescents with AS and HFA, 44 diabetic adolescents, and 250 controls completed a self-administered and validated questionnaire on quality of life, the VSP-A. Scores for adolescents with ASD were significantly lower than those of the control and the diabetic adolescents, especially for friendships, leisure time, and affective and sexual relationships. On the other hand, better scores were obtained for the relationships with parents and teachers and for self-image. Social parameters affected the quality of life of subjects with ASD, such as having friends, regularly participating in a sport, and having the support of a school carer. For subjects with autistic spectrum disorders and without mental retardation, impairment of quality of life is significant in adolescence and young adulthood. Such adolescents are dissatisfied with their relationships, although they often have real motivation to succeed with them. Relevance of VSP-A questionnaire in these special individuals is discussed.
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4. Cruz-Martin A, Crespo M, Portera-Cailliau C. {{Glutamate Induces the Elongation of Early Dendritic Protrusions via mGluRs in Wild Type Mice, but Not in Fragile X Mice}}. {PLoS One};2012;7(2):e32446.
Fragile X syndrome (FXS), the most common inherited from of autism and mental impairment, is caused by transcriptional silencing of the Fmr1 gene, resulting in the loss of the RNA-binding protein FMRP. Dendritic spines of cortical pyramidal neurons in affected individuals are abnormally immature and in Fmr1 knockout (KO) mice they are also abnormally unstable. This could result in defects in synaptogenesis, because spine dynamics are critical for synapse formation. We have previously shown that the earliest dendritic protrusions, which are highly dynamic and might serve an exploratory role to reach out for axons, elongate in response to glutamate. Here, we tested the hypothesis that this process is mediated by metabotropic glutamate receptors (mGluRs) and that it is defective in Fmr1 KO mice. Using time-lapse imaging with two-photon microscopy in acute brain slices from early postnatal mice, we find that early dendritic protrusions in layer 2/3 neurons become longer in response to application of glutamate or DHPG, a Group 1 mGluR agonist. Blockade of mGluR5 signaling, which reverses some adult phenotypes of KO mice, prevented the glutamate-mediated elongation of early protrusions. In contrast, dendritic protrusions from KO mice failed to respond to glutamate. Thus, absence of FMRP may impair the ability of cortical pyramidal neurons to respond to glutamate released from nearby pre-synaptic terminals, which may be a critical step to initiate synaptogenesis and stabilize spines.
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5. Cupic B, Hranilovic D, Jernej B, Gabrilovac J. {{Association study of genes regulating opioid system in autism}}. {Psychiatry Res};2012 (Feb 28)
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6. Davidson J, Goin-Kochel RP, Green-Snyder LA, Hundley RJ, Warren Z, Peters SU. {{Expression of the Broad Autism Phenotype in Simplex Autism Families from the Simons Simplex Collection}}. {J Autism Dev Disord};2012 (Mar 1)
The broad autism phenotype (BAP) refers to the phenotypic expression of an underlying genetic liability to autism, manifest in non-autistic relatives. This study examined the relationship among the Broad Autism Phenotype Questionnaire (BAPQ), Social Responsiveness Scale: Adult Research Version (SRS:ARV), and Family History Interview (FHI) in a large, multi-site study of 1,650 simplex families (Simons Simplex Collection). Correlations between the BAPQ and SRS:ARV Total scores were moderate, and correlations between FHI ratings and SRS:ARV and BAPQ were significant but weak. Overall, the results suggested that BAP traits occur at low rates in simplex families, and rates vary significantly depending upon the measure utilized. Implications include the need for multiple informants, and the assessment of distinct BAP traits in large-scale genetic studies of individuals with ASD.
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7. Mayo J, Eigsti IM. {{Brief Report: A Comparison of Statistical Learning in School-Aged Children with High Functioning Autism and Typically Developing Peers}}. {J Autism Dev Disord};2012 (Mar 2)
Individuals with autism spectrum disorders have impairments in language acquisition, but the underlying mechanism of these deficits is poorly understood. Implicit learning is potentially relevant to language development, particularly in speech segmentation, which relies on sensitivity to transitional probabilities between speech sounds. This study investigated the relationship between implicit learning and current language abilities in school-aged children with high functioning autism and a history of language delay (n = 17) and in children with typical development (n = 24) using a well-studied artificial language learning task. Results suggest that high functioning children with autism (HFA) and TD groups were equally able to implicitly learn transitional probabilities from a lengthy stimulus stream. Furthermore, task performance was not strongly associated with current language abilities. Implications for implicit learning research in HFA are discussed.
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8. Wang T, Bray SM, Warren ST. {{New perspectives on the biology of fragile X syndrome}}. {Curr Opin Genet Dev};2012 (Feb 28)
Fragile X syndrome (FXS) is a trinucleotide repeat disorder caused by a CGG repeat expansion in FMR1, and loss of its protein product FMRP. Recent studies have provided increased support for the role of FMRP in translational repression via ribosomal stalling and the microRNA pathway. In neurons, particular focus has been placed on identifying the signaling pathways such as PI3K and mTOR downstream of group 1 metabotropic glutamate receptors (mGluR1/5) that regulate FMRP. New evidence also suggests that loss of FMRP causes presynaptic dysfunction and abnormal adult neurogenesis. In addition, studies on FXS stem cells especially induced pluripotent stem (iPS) cells and new sequencing efforts hold out promise for deeper understanding of the silencing process and mutation spectrum of FMR1.
