1. Krishnaraj R, Ho G, Christodoulou J. {{RettBASE: Rett Syndrome Database Update}}. {Hum Mutat};2017 (May 25)
Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder that primarily affects females. Mutations in the MECP2 gene have been attributed as the major genetic cause of Rett syndrome. Recently, mutations in CDKL5 and FOXG1 genes have also been suggested to give rise to Rett syndrome, although subsequent more extensive studies suggest that diseases resulting from mutations in these two genes should be considered as distinct clinical entities. While the genetic basis for the Rett syndrome has been recognized, so far there is no effective cure for the disease and the treatments available are mainly aimed at ameliorating clinical problems associated with the disorder. The swift identification of the mutations in children is crucial for pursuing the best therapeutic care. RettBASE was created in 2002 as a MECP2 variant database and has grown to become a comprehensive variant database for Rett syndrome and related clinical phenotypes, containing a curated collection of variants for MECP2, CDKL5 and FOXG1 genes. Here we describe the development and growth of RettBASE after its inception in 2001. Currently, RettBASE holds a total of 4668 variants in MECP2, 498 variants in CDKL5 and 64 variants in FOXG1. This article is protected by copyright. All rights reserved.
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2. Rudra A, Belmonte MK, Soni PK, Banerjee S, Mukerji S, Chakrabarti B. {{Prevalence of autism spectrum disorder and autistic symptoms in a school-based cohort of children in Kolkata, India}}. {Autism Res};2017 (May 25)
Despite housing approximately 18% of the world’s population, India does not yet have an estimate of prevalence of autism. This study was carried out to estimate the prevalence of autism in a selected population of school-children in India. N = 11,849 children (mean age = 5.9 [SD = 1.3], 39.5% females) were selected from various school types from three boroughs in Kolkata, India. Parents/caregivers and teachers filled in the social and communication disorders checklist (SCDC). Children meeting cutoff on parent-reported SCDC were followed up with the social communication questionnaire (SCQ). SCQ-positive children were administered the autism diagnostic observation schedule (ADOS). Teacher report on SCDC was available on all 11,849 children. Parent-report SCDC scores were obtained for 5,947 children. Mean scores on teacher SCDC were significantly lower than parent SCDC. Out of 1,247 SCDC-positive children, 882 answered the SCQ, of whom 124 met the cutoff score of 15. Six of these children met criteria for autism, autism spectrum disorder (ASD), or broader autism spectrum on the ADOS. The weighted estimate of supra-threshold SCQ scores was 3.54% (CI: 2.88-4.3%). The weighted prevalence estimate of positive scores (for broader autism spectrum + ASD + autism) was 0.23% (0.07-0.46%). As approximately 20% children in this state are known to be out of the school system, and ASD prevalence is likely to be higher in this group, this estimate is likely to represent the lower-bound of the true prevalence. This study provides preliminary data on the prevalence of broader-spectrum autism and supra-threshold autistic traits in a population sample of school children in Eastern India. Autism Res 2017. (c)2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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3. Shou G, Mosconi MW, Wang J, Ethridge LE, Sweeney JA, Ding L. {{Electrophysiological signatures of atypical intrinsic brain connectivity networks in autism}}. {J Neural Eng};2017 (May 25);14(4):046010.
OBJECTIVE: Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network. APPROACH: Connectivity within individual ICNs (measured by spectral power) and between ICNs (measured by coherence) were examined at four canonical frequency bands via a time-frequency independent component analysis on high-density EEG, which were recorded from 20 ASD and 20 typical developing (TD) subjects during an eyes-closed resting state. MAIN RESULTS: Among twelve identified electrophysiological ICNs, individuals with ASD showed hyper-connectivity in individual ICNs and hypo-connectivity between ICNs. Functional connectivity alterations in ASD were more severe in the frontal lobe and the default mode network (DMN) and at low frequency bands. These functional connectivity measures also showed abnormal age-related associations in ICNs related to frontal, temporal and motor regions in ASD. SIGNIFICANCE: Our findings suggest that ASD is characterized by the opposite directions of abnormalities (i.e. hypo- and hyper-connectivity) in the hierarchical structure of the whole brain network, with more impairments in the frontal lobe and the DMN at low frequency bands, which are critical for top-down control of sensory systems, as well as for both cognition and social skills.
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4. Stratis EA, Lecavalier L. {{Predictors of Parent-Teacher Agreement in Youth with Autism Spectrum Disorder and Their Typically Developing Siblings}}. {J Autism Dev Disord};2017 (May 25)
This study evaluated the magnitude of informant agreement and predictors of agreement on behavior and emotional problems and autism symptoms in 403 children with autism and their typically developing siblings. Parent-teacher agreement was investigated on the Child Behavior Checklist (CBCL) and Social Responsiveness Scale (SRS). Agreement between parents and teachers fell in the low to moderate range. Multiple demographic and clinical variables were considered as predictors, and only some measures of parent broad autism traits were associated with informant agreement. Parent report on the SRS was a positive predictor of agreement, while teacher report was a negative predictor. Parent report on the CBCL emerged as a positive predictor of agreement, while teacher report emerged as a negative predictor.
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5. Weinstein V, Tanpaiboon P, Chapman KA, Ah Mew N, Hofherr S. {{Do the data really support ordering fragile X testing as a first-tier test without clinical features?}}. {Genet Med};2017 (May 25)
PurposeCurrent guidelines recommend first-tier chromosome microarray analysis (CMA) and fragile X syndrome (FX) testing for males with isolated intellectual disabilities/learning delay (ID/LD) and autism spectrum disorders (ASDs).MethodsMales in our clinic with ID/LD or ASD (310) were analyzed for positive results from CMA and/or FX testing.ResultsCMA detected abnormalities in 29% of males with ID/LD and only 9% of males with ASD (including variants of uncertain significance and absence of heterozygosity). When males with ID/LD were tested for FX, the detection rate was 2.5% (2 of 80). Both patients had dysmorphic features and maternal family history. No males with ASD had positive FX test results.ConclusionsThe detection rate of CMA in males with isolated ID/LD in this study was higher than in the literature (10-20%). CMA results for males with ASD (9%) and FX testing for males with ID/LD (2.5%) overlap with the literature (7-10% and 2%, respectively). The yield of FX testing for patients with ASD was zero, which is close to that of the literature (0.5-2%). These results suggest that FX testing as a first-tier test may not be necessary, unless other criteria suggest FX.GENETICS in MEDICINE advance online publication, 25 May 2017; doi:10.1038/gim.2017.64.
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6. Whitehouse AJO, Granich J, Alvares G, Busacca M, Cooper MN, Dass A, Duong T, Harper R, Marshall W, Richdale A, Rodwell T, Trembath D, Vellanki P, Moore DW, Anderson A. {{A randomised controlled trial of an iPad-based application to complement early behavioural intervention in Autism Spectrum Disorder}}. {J Child Psychol Psychiatry};2017 (May 25)
BACKGROUND: Technology-based interventions for Autism Spectrum Disorder (ASD) have proliferated, but few have been evaluated within the context of a randomised controlled trial (RCT). This RCT evaluated the efficacy of one technology-based early intervention programme (Therapy Outcomes By You; TOBY) in young children with ASD. METHODS: TOBY is an app-based learning curriculum designed for children and parents as a complement to early behavioural intervention. Eighty children (16 female) were recruited to this RCT within 12 months of receiving a diagnosis of ASD (M age = 3.38; SD = 0.69) and randomised to receive either treatment-as-usual (community-based intervention, n = 39) or the TOBY therapy (at least 20 min/day) plus treatment-as-usual (n = 41) for a period of 6 months. Outcomes were assessed at 3 and 6 months postbaseline. (Australian New Zealand Clinical Trials Registry: ACTRN12614000738628; www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365463). RESULTS: Children in the TOBY intervention group averaged 19 min/day engaging with the app in the first 3 months, but only 2 min/day during the second 3 months. There was no group difference in scores on the primary outcome, the Autism Treatment Evaluation Checklist, at either the 3- or 6-month follow-up. However, significant improvements at the 6-month follow-up were observed in the TOBY intervention group relative to the treatment-as-usual group on three secondary outcomes: the Fine Motor and Visual Reception subscales of the Mullen Scale of Early Learning and the Total Words Understood scale of the MacArthur-Bates Communicative Development Index. Statistical trends towards improvement in the TOBY intervention group were observed on measures of adaptive function, although these decreased in magnitude from the 3- to 6-month follow-up. CONCLUSIONS: This study provides evidence that technology-based interventions may provide a relatively low-cost addition to existing therapist-delivered interventions for children with ASD. However, sustained use of the app over the full 6-month period was a challenge for most families.
