1. Bailey DB, Jr., Raspa M, Wheeler AC, Edwards A, Bishop E, Bann C, Borasky D, Appelbaum PS. {{Parent Ratings of Ability to Consent for Clinical Trials in Fragile X Syndrome}}. {J Empir Res Hum Res Ethics}. 2014; 9(3): 18-28.
Advances in understanding neurobiology and intellectual disabilities have led to clinical trials testing new medications. This study assessed parents’ perceptions of the ability of their son or daughter with fragile X syndrome (FXS), an inherited form of intellectual disability, to participate in the consent process for clinical trials. Four hundred and twenty-two families participated in a survey that included six items assessing various aspects of the ability to provide consent. A rank ordering of decisional tasks was found. The easiest task was to understand that the medication was different from his or her medical treatment; the most difficult was the ability to understand and weigh the potential benefits and risks of study participation. Factor analysis suggested that despite the range in difficulty, the six items were best summarized by a single decisional ability score. Parents of 29% of males reported that their son was not at all capable of participating, but the remainder exhibited a range of decisional skills. Factors associated with this variability include age, and parents’ willingness to enroll their child in clinical trials. We conclude that many individuals with FXS appear to be able to participate at some level in the consent or assent process, but will likely need individualized support to maximize effective participation.
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2. Bowers K, Lin PI, Erickson C. {{Pharmacogenomic Medicine in Autism: Challenges and Opportunities}}. {Paediatr Drugs}. 2014.
Autism spectrum disorder (ASD) affects 1 in 68 children in the US and is distinguished by core deficits in social interactions. Developing pharmacologic treatments for ASD is complicated by clinical and genetic heterogeneity. Although pharmacological treatments have not been shown to be effective in treating the core symptoms of ASD (i.e., social deficits), there is evidence that the burden of emotional and behavioral problems can be reduced with pharmacotherapy. Numerous randomized clinical trials of treatments for the core ASD deficits have been conducted; however, most have provided inconclusive results due to the substantial variation in treatment response. Variation also exists in the considerable metabolic side effects of many of the current treatments. Some of this variation may be explained by differences in the underlying genetic pathways. Exploiting the link between genetic heterogeneity and clinical variation associated with behavioral problems may provide an opportunity for targeted treatment of ASD. In this review, we summarize the recent findings from pharmacogenomics studies of ASD and suggest further how understanding how genetic liability modifies the effect of drugs may present an opportunity to address the challenges of personalized medicine in autism.
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3. Buijsen RA, Sellier C, Severijnen LA, Oulad-Abdelghani M, Verhagen RF, Berman RF, Charlet-Berguerand N, Willemsen R, Hukema RK. {{FMRpolyG-positive inclusions in CNS and non-CNS organs of a fragile X premutation carrier with fragile X-associated tremor/ataxia syndrome}}. {Acta Neuropathol Commun}. 2014; 2(1): 162.
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4. Dachtler J, Glasper J, Cohen RN, Ivorra JL, Swiffen DJ, Jackson AJ, Harte MK, Rodgers RJ, Clapcote SJ. {{Deletion of alpha-neurexin II results in autism-related behaviors in mice}}. {Transl Psychiatry}. 2014; 4: e484.
Autism is a common and frequently disabling neurodevelopmental disorder with a strong genetic basis. Human genetic studies have discovered mutations disrupting exons of the NRXN2 gene, which encodes the synaptic adhesion protein alpha-neurexin II (Nrxn2alpha), in two unrelated individuals with autism, but a causal link between NRXN2 and the disorder remains unclear. To begin to test the hypothesis that Nrxn2alpha deficiency contributes to the symptoms of autism, we employed Nrxn2alpha knockout (KO) mice that genetically model Nrxn2alpha deficiency in vivo. We report that Nrxn2alpha KO mice displayed deficits in sociability and social memory when exposed to novel conspecifics. In tests of exploratory activity, Nrxn2alpha KO mice displayed an anxiety-like phenotype in comparison with wild-type littermates, with thigmotaxis in an open field, less time spent in the open arms of an elevated plus maze, more time spent in the enclosure of an emergence test and less time spent exploring novel objects. However, Nrxn2alpha KO mice did not exhibit any obvious changes in prepulse inhibition or in passive avoidance learning. Real-time PCR analysis of the frontal cortex and hippocampus revealed significant decreases in the mRNA levels of genes encoding proteins involved in both excitatory and inhibitory transmission. Quantification of protein expression revealed that Munc18-1, encoded by Stxbp1, was significantly decreased in the hippocampus of Nrxn2alpha KO mice, which is suggestive of deficiencies in presynaptic vesicular release. Our findings demonstrate a causal role for the loss of Nrxn2alpha in the genesis of autism-related behaviors in mice.
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5. Fitzgerald J, Johnson K, Kehoe E, Bokde AL, Garavan H, Gallagher L, McGrath J. {{Disrupted Functional Connectivity in Dorsal and Ventral Attention Networks During Attention Orienting in Autism Spectrum Disorders}}. {Autism Res}. 2014.
BACKGROUND: Attention orienting is a cognitive process that facilitates the movement of attention focus from one location to another: this may be impaired in autism spectrum disorder (ASD). Dorsal and ventral attention networks (DAN and VAN) sub-serve the process of attention orienting. This study investigated the functional connectivity of attention orienting in these networks in ASD using the Posner Cueing Task. METHOD: Twenty-one adolescents with ASD and 21 age and IQ matched controls underwent functional magnetic resonance imaging. A psychophysical interaction (PPI) analysis was implemented to investigate task-dependent functional connectivity, measuring synchronicity of brain regions during the task. Regions of interest (ROI) were selected to explore functional connectivity in the DAN during cue-only conditions and in the VAN during invalid and valid trials. RESULTS: Behaviourally, the ASD and control groups performed the task in a similar manner. Functional MRI results indicated that the ASD and control groups activated similar brain regions. During invalid trials (VAN), the ASD group showed significant positive functional connectivity to multiple brain regions, whilst the control group demonstrated negative connectivity. During valid trials (VAN), the two groups also showed contrasting patterns of connectivity. In the cue-only conditions (DAN), the ASD group showed weaker functional connectivity. CONCLUSION: The DAN analysis suggests that the ASD group has weaker coherence between brain areas involved in goal-driven, endogenous attention control. The strong positive functional connectivity exhibited by the ASD group in the VAN during the invalid trials suggests that individuals with ASD may generate compensatory mechanisms to achieve neurotypical behaviour. These results support the theory of abnormal cortical connectivity in autism. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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6. Gkogkas CG, Khoutorsky A, Cao R, Jafarnejad SM, Prager-Khoutorsky M, Giannakas N, Kaminari A, Fragkouli A, Nader K, Price TJ, Konicek BW, Graff JR, Tzinia AK, Lacaille JC, Sonenberg N. {{Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X Syndrome-like Phenotypes}}. {Cell Rep}. 2014.
Fragile X syndrome (FXS) is the leading genetic cause of autism. Mutations in Fmr1 (fragile X mental retardation 1 gene) engender exaggerated translation resulting in dendritic spine dysmorphogenesis, synaptic plasticity alterations, and behavioral deficits in mice, which are reminiscent of FXS phenotypes. Using postmortem brains from FXS patients and Fmr1 knockout mice (Fmr1-/y), we show that phosphorylation of the mRNA 5′ cap binding protein, eukaryotic initiation factor 4E (eIF4E), is elevated concomitant with increased expression of matrix metalloproteinase 9 (MMP-9) protein. Genetic or pharmacological reduction of eIF4E phosphorylation rescued core behavioral deficits, synaptic plasticity alterations, and dendritic spine morphology defects via reducing exaggerated translation of Mmp9 mRNA in Fmr1-/y mice, whereas MMP-9 overexpression produced several FXS-like phenotypes. These results uncover a mechanism of regulation of synaptic function by translational control of Mmp-9 in FXS, which opens the possibility of new treatment avenues for the diverse neurological and psychiatric aspects of FXS.
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7. Globerson E, Amir N, Kishon-Rabin L, Golan O. {{Prosody Recognition in Adults With High-Functioning Autism Spectrum Disorders: From Psychoacoustics to Cognition}}. {Autism Res}. 2014.
Prosody is an important tool of human communication, carrying both affective and pragmatic messages in speech. Prosody recognition relies on processing of acoustic cues, such as the fundamental frequency of the voice signal, and their interpretation according to acquired socioemotional scripts. Individuals with autism spectrum disorders (ASD) show deficiencies in affective prosody recognition. These deficiencies have been mostly associated with general difficulties in emotion recognition. The current study explored an additional association between affective prosody recognition in ASD and auditory perceptual abilities. Twenty high-functioning male adults with ASD and 32 typically developing male adults, matched on age and verbal abilities undertook a battery of auditory tasks. These included affective and pragmatic prosody recognition tasks, two psychoacoustic tasks (pitch direction recognition and pitch discrimination), and a facial emotion recognition task, representing nonvocal emotion recognition. Compared with controls, the ASD group demonstrated poorer performance on both vocal and facial emotion recognition, but not on pragmatic prosody recognition or on any of the psychoacoustic tasks. Both groups showed strong associations between psychoacoustic abilities and prosody recognition, both affective and pragmatic, although these were more pronounced in the ASD group. Facial emotion recognition predicted vocal emotion recognition in the ASD group only. These findings suggest that auditory perceptual abilities, alongside general emotion recognition abilities, play a significant role in affective prosody recognition in ASD. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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8. Hagerman RJ. {{The Fragile X Mouse is Cured, Now for the Patients}}. {Hum Mutat}. 2014; 35(12): v.
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9. Luo S, Huang W, Xia Q, Xia Y, Du Q, Wu L, Duan R. {{Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with Fragile X Syndrome: case report}}. {BMC Med Genet}. 2014; 15(1): 125.
BackgroundIncreasing number of case reports of mosaic mutations and deletions have better armed clinicians and geneticists with more accurate and focused prenatal diagnoses. Since mosaicism means a significant increase of recurrence risk, detailed parental profiling is essential for risk assessments.Case presentationWe here describe a clinically unaffected mother with a son who had fragile X syndrome (FXS) caused by a large deletion that includes the entire FMR1. To assess the recurrence risk regarding her second pregnancy, a series of genetic tests were conducted to establish this mother inverted question marks status. Routine single nucleotide polymorphism (SNP) array and fluorescence in situ hybridisation (FISH) analyses detected two normal FMR1 copies in her blood. However, in-depth studies across the deleted region revealed varying proportions of mosaic deletion in her somatic tissues: lowest in the blood, moderately higher in the skin, urine sediment and menstrual discharge and highest in her eyebrow. Further FISH analysis of her skin-derived fibroblasts confirmed mosaicism of 13%.ConclusionTo our knowledge, this is the first characterized case of a female who was mosaic for an FMR1 deletion and extensive investigation of her mosaic status provided valuable information for her reproduction choices. Our case report may also alert clinicians and geneticists that a cryptic mosaicism with somatic heterogeneity should be carefully considered in families with children having clinically defined `de novo inverted question mark mutations, to avoid a second pregnancy with identical genetic abnormalities.
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10. Maillard AM, Ruef A, Pizzagalli F, Migliavacca E, Hippolyte L, Adaszewski S, Dukart J, Ferrari C, Conus P, Mannik K, Zazhytska M, Siffredi V, Maeder P, Kutalik Z, Kherif F, Hadjikhani N, Beckmann JS, Reymond A, Draganski B, Jacquemont S. {{The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity}}. {Mol Psychiatry}. 2014.
Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy.Molecular Psychiatry advance online publication, 25 November 2014; doi:10.1038/mp.2014.145.
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11. Mamidala MP, Kalikiri MK, P TVP, Rajesh N, Vallamkonda OR, Rajesh V. {{Consanguinity in India and Its Association With Autism Spectrum Disorder}}. {Autism Res}. 2014.
Autism Spectrum Disorder (ASD) has both genetic and environmental factors in its etiology. The risk for many disorders is increased by consanguinity, but it is not known whether it increases the risk for ASD. Our study from large population in India concludes that consanguinity increases the risk for ASD with an odds ratio of 3.22. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
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12. Merikangas AK, Segurado R, Heron EA, Anney RJ, Paterson AD, Cook EH, Pinto D, Scherer SW, Szatmari P, Gill M, Corvin AP, Gallagher L. {{The phenotypic manifestations of rare genic CNVs in autism spectrum disorder}}. {Mol Psychiatry}. 2014.
Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on the diagnosis of ASD. There is limited understanding of the impact of CNVs on the ‘sub-phenotypes’ of ASD. The objective of this paper is to evaluate associations between CNVs in differentially brain expressed (DBE) genes or genes previously implicated in ASD/intellectual disability (ASD/ID) and specific sub-phenotypes of ASD. The sample consisted of 1590 cases of European ancestry from the Autism Genome Project (AGP) with a diagnosis of an ASD and at least one rare CNV impacting any gene and a core set of phenotypic measures, including symptom severity, language impairments, seizures, gait disturbances, intelligence quotient (IQ) and adaptive function, as well as paternal and maternal age. Classification analyses using a non-parametric recursive partitioning method (random forests) were employed to define sets of phenotypic characteristics that best classify the CNV-defined groups. There was substantial variation in the classification accuracy of the two sets of genes. The best variables for classification were verbal IQ for the ASD/ID genes, paternal age at birth for the DBE genes and adaptive function for de novo CNVs. CNVs in the ASD/ID list were primarily associated with communication and language domains, whereas CNVs in DBE genes were related to broader manifestations of adaptive function. To our knowledge, this is the first study to examine the associations between sub-phenotypes and CNVs genome-wide in ASD. This work highlights the importance of examining the diverse sub-phenotypic manifestations of CNVs in ASD, including the specific features, comorbid conditions and clinical correlates of ASD that comprise underlying characteristics of the disorder.Molecular Psychiatry advance online publication, 25 November 2014; doi:10.1038/mp.2014.150.
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13. Nambisan P, Lamkin D, DeLong C. {{Feasibility, benefits and challenges of using telemonitoring for the aging with Developmental Disabilities (DD): An exploratory study}}. {Online J Public Health Inform}. 2014; 6(2): e186.
Telemonitoring is being increasingly used to provide services to patients with developmental disabilities in residential community settings. The objective of this study is to assess the feasibility, benefits and challenges of using telemonitoring for aging patients with developmental disabilities. We also assess the benefits and challenges of telemonitoring for the caregivers of these patients. Focus groups and questionnaire-based surveys were used to collect data from patients and caregivers. The study found that telemonitoring was feasible and beneficial for the aging with developmental disabilities, albeit for those who are moderate to high functioning. It was not beneficial or feasible for those with very low functional capabilities. The study found that telemonitoring was beneficial towards providing more independence, more self-confidence in carrying out daily activities, and more knowledge regarding their disease. The study also found that telemonitoring was useful for caregivers to better understand their patients and their needs, better coordinate the services delivered, and to enhance the satisfaction of caregiving. The discussions include limitations of using quantitative methods in this type of setting.
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14. Provenzano G, Pangrazzi L, Poli A, Sgado P, Berardi N, Bozzi Y. {{Reduced phosphorylation of synapsin I in the hippocampus of Engrailed-2 knockout mice, a model for autism spectrum disorders}}. {Neuroscience}. 2014.
Mice lacking the homeodomain transcription factor Engrailed-2 (En2-/- mice) are a well-characterized model for autism spectrum disorders (ASD). En2-/- mice present molecular, neuropathological and behavioral deficits related to ASD, including down-regulation of ASD-associated genes, cerebellar hypoplasia, interneuron loss, enhanced seizure susceptibility, decreased sociability and impaired cognition. Specifically, impaired spatial learning in the Morris water maze (MWM) is associated with reduced expression of neurofibromin and increased phosphorylation of extracellular-regulated kinase (ERK) in the hippocampus of En2-/- adult mice. In the attempt to better understand the molecular cascades underlying neurofibromin-dependent cognitive deficits in En2 mutant mice, we investigated the expression and phosphorylation of synapsin I (SynI; a major target of neurofibromin-dependent signaling) in the hippocampus of wild-type (WT) and En2-/- mice before and after MWM. Here we show that SynI mRNA and protein levels are down-regulated in the hippocampus of naive and MWM-treated En2-/- mice, as compared to WT controls. This down-regulation is paralleled by reduced levels of SynI phosphorylation at Ser549 and Ser553 residues in the hilus of mutant mice, before and after MWM. These data indicate that in En2-/- hippocampus, neurofibromin-dependent pathways converging on SynI phosphorylation might underlie hippocampal-dependent learning deficits observed in En2-/- mice.
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15. Shpyleva S, Ivanovsky S, de Conti A, Melnyk S, Tryndyak V, Beland FA, James SJ, Pogribny IP. {{Cerebellar Oxidative DNA Damage and Altered DNA Methylation in the BTBR T+tf/J Mouse Model of Autism and Similarities with Human Post Mortem Cerebellum}}. {PLoS One}. 2014; 9(11): e113712.
The molecular pathogenesis of autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism. In this study we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of autism, and from human post-mortem cerebellum of individuals with autism, are both characterized by an increased levels of 8-oxo-7-hydrodeoxyguanosine (8-oxodG), 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC). The increase in 8-oxodG and 5mC content was associated with a markedly reduced expression of the 8-oxoguanine DNA-glycosylase 1 (Ogg1) and increased expression of de novo DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b). Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1) and Tet2 genes, but significantly correlated with the presence of 8-oxodG in DNA. This finding and similar elevation in 8-oxodG in cerebellum of individuals with autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of OGG1 alterations in pathogenesis of autism.
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16. Tovar AT, Fein D, Naigles LR. {{Grammatical Aspect Is A Strength in the Language Comprehension of Young Children with Autism}}. {J Speech Lang Hear Res}. 2014.
Purpose: The comprehension of tense/aspect morphology by children with ASD was assessed via Intermodal Preferential Looking (IPL) to determine whether this population’s difficulties with producing these morphemes extended to their comprehension. Method: Four-year-old participants were assessed twice, four months apart. They viewed a video which presented side-by-side ongoing and completed events paired with familiar verbs with past tense and progressive morphology. Their eye movements were recorded and coded offline; the IPL measures included percentage of looking time at, and latency of first look to, the matching scene. Spontaneous speech samples were also obtained, and coded for number of words, past tense, and progressive inflections. Results: Relative to their baseline preferences, these four-year-old children with ASD looked more quickly to and longer at the matching scene for both morphemes. Children who produced more words, progressive, and past morphemes, as well as who performed better on standardized language assessments, demonstrated better comprehension of -ing. Conclusion: Overall these children with ASD demonstrated consistent comprehension of grammatical aspect morphology; moreover, their degree of comprehension was found to correlate with spontaneous production and standardized test scores.
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17. Urbanowicz A, Downs J, Girdler S, Ciccone N, Leonard H. {{Aspects of speech-language abilities are influenced by MECP2 mutation type in girls with Rett syndrome}}. {Am J Med Genet A}. 2014.
This study investigates relationships between methyl-CpG-binding protein 2 gene (MECP2) mutation type and speech-language abilities in girls with Rett syndrome. Cross-sectional data on 766 girls, aged 15 years and under, with genetically confirmed Rett syndrome was obtained from the Australian Rett Syndrome Database (ARSD) (n = 244) and the International Rett Syndrome Phenotype Database (InterRett) (n = 522). Relationships between MECP2 mutation type and age of regression in speech-language abilities, and the level of speech-language abilities before and after this regression were investigated. The females had a median age of 4.95 years in the ARSD and 5.25 years in InterRett. The majority (89%, 685/766) acquired speech-language abilities in the form of babble or words at some point in time. Of those who acquired babble or words, 85% (581/685) experienced a regression in these abilities. Those with a p.Arg133Cys mutation were the most likely to use one or more words, prior to (RRR = 3.45; 95% CI 1.15-10.41) and after (RRR = 5.99; 95% CI 2.00-17.92), speech-language regression. Girls with Rett syndrome vary in their use of speech and language, and in their experience of speech-language regression and these variations are partly explained by genotype. (c) 2014 Wiley Periodicals, Inc.
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18. Williamson SL, Ellaway CJ, Peters GB, Pelka GJ, Tam PP, Christodoulou J. {{Deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in twins with a Rett syndrome-like phenotype}}. {Eur J Hum Genet}. 2014.
Rett syndrome (RTT), a neurodevelopmental disorder that predominantly affects females, is primarily caused by variants in MECP2. Variants in other genes such as CDKL5 and FOXG1 are usually associated with individuals who manifest distinct phenotypes that may overlap with RTT. Individuals with phenotypes suggestive of RTT are typically screened for variants in MECP2 and then subsequently the other genes dependent on the specific phenotype. Even with this screening strategy, there are individuals in whom no causative variant can be identified, suggesting that there are other novel genes that contribute to the RTT phenotype. Here we report a de novo deletion of protein tyrosine phosphatase, non-receptor type 4 (PTPN4) in identical twins with a RTT-like phenotype. We also demonstrate the reduced expression of Ptpn4 in a Mecp2 null mouse model of RTT, as well as the activation of the PTPN4 promoter by MeCP2. Our findings suggest that PTPN4 should be considered for addition to the growing list of genes that warrant screening in individuals with a RTT-like phenotype.European Journal of Human Genetics advance online publication, 26 November 2014; doi:10.1038/ejhg.2014.249.
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19. Zhang QB, Gao SJ, Zhao HX. {{Thioredoxin: A novel, independent diagnosis marker in children with autism}}. {Int J Dev Neurosci}. 2014.
BACKGROUND: Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in Autism spectrum disorders (ASD). METHODS: Eighty patients diagnosed with ASD and 100 sex and age matched typically developing children were assessed for serum TRX content at admission. TRX were assayed with solid-phase sandwich ELISA, and severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS) Score. RESULTS: The results indicated that the median serum TRX levels were significantly (P<0.0001) higher in children with ASD as compared to typically developing children [17.9(IQR: 10.7-25.8)ng/ml and 5.5(3.6-9.2)ng/ml, respectively]. Levels of TRX increased with increasing severity of ASD as defined by the CARS score. After adjusting for all other possible covariates, TRX still was an independent diagnosis marker of ASD with an adjusted OR of 1.454 (95% CI, 1.232-1.892; P<0.0001). Based on the receiver operating characteristic (ROC) curve, the optimal cut-off value of serum TRX levels as an indicator for auxiliary diagnosis of autism was projected to be 10.6ng/ml. Further, we found that an increased diagnosis of ASD was associated with TRX levels >/=10.6ng/ml (adjusted OR 15.31, 95% CI: 7.36-31.85) after adjusting for possible confounders. CONCLUSIONS: Our study demonstrated that serum TRX levels were associated with ASD, and elevated levels could be considered as a novel, independent diagnosis indicator of ASD.
