1. Bartlett CW, Hou L, Flax JF, Hare A, Cheong SY, Fermano Z, Zimmerman-Bier B, Cartwright C, Azaro MA, Buyske S, Brzustowicz LM. {{A Genome Scan for Loci Shared by Autism Spectrum Disorder and Language Impairment}}. {Am J Psychiatry}. 2013.
OBJECTIVE The authors conducted a genetic linkage study of families that have both autism spectrum disorder (ASD) and language-impaired probands to find common communication impairment loci. The hypothesis was that these families have a high genetic loading for impairments in language ability, thus influencing the language and communication deficits of the family members with ASD. Comprehensive behavioral phenotyping of the families also enabled linkage analysis of quantitative measures, including normal, subclinical, and disordered variation in all family members for the three general autism symptom domains: social, communication, and compulsive behaviors. METHOD The primary linkage analysis coded persons with either ASD or specific language impairment as « affected. » The secondary linkage analysis consisted of quantitative metrics of autism-associated behaviors capturing normal to clinically severe variation, measured in all family members. RESULTS Linkage to language phenotypes was established at two novel chromosomal loci, 15q23-26 and 16p12. The secondary analysis of normal and disordered quantitative variation in social and compulsive behaviors established linkage to two loci for social behaviors (at 14q and 15q) and one locus for repetitive behaviors (at 13q). CONCLUSION These data indicate shared etiology of ASD and specific language impairment at two novel loci. Additionally, nonlanguage phenotypes based on social aloofness and rigid personality traits showed compelling evidence for linkage in this study group. Further genetic mapping is warranted at these loci.
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2. Basu S, Parry P. {{The autism spectrum disorder ‘epidemic’: Need for biopsychosocial formulation}}. {Aust N Z J Psychiatry}. 2013.
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3. Briggs A. {{Primary care of a child with Rett syndrome}}. {J Am Assoc Nurse Pract}. 2013.
PURPOSE: To discuss the history, incidence, pathophysiology, diagnostic criteria, disease staging, clinical presentation and physical exam findings, and role of the primary care provider (PCP) as they pertain to care for a child with Rett syndrome (RS). DATA SOURCES: Review of published literature on and diagnostic criteria of RS. CONCLUSIONS: RS is a devastating X-linked neurodevelopmental disorder that affects females and a small percentage of males. RS is characterized by stereotypic wringing hand movements, social withdrawal, communication dysfunction, cognitive impairment, respiratory dysfunction, and failing locomotion. Diagnosis is generally made clinically despite available genetic testing. Advances in research have been beneficial; however, the pathophysiology of RS has proven to be elusive. RS is a complex disease that involves multiple organ systems. IMPLICATIONS FOR PRACTICE: PCPs need to be aware of how to manage RS patients if they present to the primary care office, and need to be prepared to diagnose RS early, provide appropriate interventions and referrals, understand the challenges, and understand the goal of treatment. They also should be able to provide continuity of care, provide anticipatory guidance, and engage in shared decision with families and patients.
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4. Jacquemont S, Berry-Kravis E, Hagerman R, von Raison F, Gasparini F, Apostol G, Ufer M, Des Portes V, Gomez-Mancilla B. {{The challenges of clinical trials in fragile X syndrome}}. {Psychopharmacology (Berl)}. 2013.
RATIONALE: Advances in understanding the underlying mechanisms of conditions such as fragile X syndrome (FXS) and autism spectrum disorders have revealed heterogeneous populations. Recent trials of novel FXS therapies have highlighted several challenges including subpopulations with possibly differential therapeutic responses, the lack of specific outcome measures capturing the full range of improvements of patients with FXS, and a lack of biomarkers that can track whether a specific mechanism is responsive to a new drug and whether the response correlates with clinical improvement. OBJECTIVES: We review the phenotypic heterogeneity of FXS and the implications for clinical research in FXS and other neurodevelopmental disorders. RESULTS: Residual levels of fragile X mental retardation protein (FMRP) expression explain in part the heterogeneity in the FXS phenotype; studies indicate a correlation with both cognitive and behavioral deficits. However, this does not fully explain the extent of phenotypic variance observed or the variability of drug response. Post hoc analyses of studies involving the selective mGluR5 antagonist mavoglurant and the GABAB agonist arbaclofen have uncovered significant therapeutic responses following patient stratification according to FMR1 promoter methylation patterns or baseline severity of social withdrawal, respectively. Future studies designed to quantify disease modification will need to develop new strategies to track changes effectively over time and in multiple symptom domains. CONCLUSION: Appropriate selection of patients and outcome measures is central to optimizing future clinical investigations of these complex disorders.
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5. Kievit RA, Geurts HM. {{Autism and perception of awareness in self and others: Two sides of the same coin or dissociated abilities?}}. {Cogn Neurosci}. 2011; 2(2): 119-20.
Abstract Graziano and Kastner propose a theoretical framework suggesting that the same cognitive machinery underlies computation and inferences concerning (the content of) awareness in others as underlies the perception of the contents of our own awareness. We draw from this hypothesis a strong prediction: Individuals who have deficiencies in one of these abilities must also be impaired in the other. We discuss evidence supporting this prediction from the literature on autism spectrum disorder, but also discuss tentative evidence for a possible dissociation between these two abilities. We conclude that these lines of evidence form crucial empirical tests of the theory.
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6. Lindsay AJ, McCaffrey MW. {{Myosin Va is Required for the Transport of Fragile X Mental Retardation Protein (FMRP) Granules}}. {Biol Cell}. 2013.
Background information. Fragile X Mental Retardation Protein (FMRP) is a selective RNA binding protein that functions as a translational inhibitor. It also plays a role in directing the transport of a subset of mRNAs to their site of translation and several recent reports have implicated microtubule motor proteins in the transport of FMRP-messenger ribonucleoprotein (mRNP) granules in neurons. Earlier work reported the association of the actin-based motor protein myosin Va with FMRP granules. Results. Here we follow up on this finding and confirm that myosin Va does in fact associate with FMRP and is required for its correct intracellular localisation. FMRP is concentrated in the perinuclear region of myosin Va-null mouse melanoma cells which contrasts starkly with the evenly distributed punctate pattern observed in wild-type cells. Similarly, overexpression of a dominant-negative mutant of myosin Va results in the accumulation of FMRP in large aggregate-like structures. FRAP experiments demonstrate that FMRP is largely immobile in the absence of myosin Va. Conclusions. Combining this data we propose a model in which myosin Va and kinesin play key roles in the assembly and subsequent transport of FMRP granules along microtubules to the periphery of the cell. Myosin Va captures the complex onto peripheral actin structures and mediates the local delivery of the FMRP granule to the site of mRNA translation. This article is protected by copyright. All rights reserved.
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7. Mitterauer BJ. {{Intuition in autistic savantism: A hypothetical model based on glial-neuronal interactions}}. {Med Hypotheses}. 2013.
The previously proposed hypothesis on the astrocyte mega-domains of autistic savantism is here further elaborated with regard to the faculty of intuition. Two mechanisms may essentially be responsible for the intuition of autistic savantism. First, the increased number of contacted synapses via the astrocyte processes enables the brain to generate a comprehensive perception of a scene in the environment. Second, to inhibit a further reflection process neuronal synapses responsible for pertinent information must be rejected by retraction of the same astrocyte processes. This second mechanism may exert the disconnections of neuronal systems and is experimentally verified. Therefore, the break-off of further social contacts may also be necessary. The testing of the hypothesis in living brains is difficult but at least partly possible in post-mortem brains.
