1. Bacchelli E, Battaglia A, Cameli C, Lomartire S, Tancredi R, Thomson S, Sutcliffe JS, Maestrini E. {{Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility}}. {Am J Med Genet A};2015 (Feb 5)
Chromosome 15q13.3 recurrent microdeletions are causally associated with a wide range of phenotypes, including autism spectrum disorder (ASD), seizures, intellectual disability, and other psychiatric conditions. Whether the reciprocal microduplication is pathogenic is less certain. CHRNA7, encoding for the alpha7 subunit of the neuronal nicotinic acetylcholine receptor, is considered the likely culprit gene in mediating neurological phenotypes in 15q13.3 deletion cases. To assess if CHRNA7 rare variants confer risk to ASD, we performed copy number variant analysis and Sanger sequencing of the CHRNA7 coding sequence in a sample of 135 ASD cases. Sequence variation in this gene remains largely unexplored, given the existence of a fusion gene, CHRFAM7A, which includes a nearly identical partial duplication of CHRNA7. Hence, attempts to sequence coding exons must distinguish between CHRNA7 and CHRFAM7A, making next-generation sequencing approaches unreliable for this purpose. A CHRNA7 microduplication was detected in a patient with autism and moderate cognitive impairment; while no rare damaging variants were identified in the coding region, we detected rare variants in the promoter region, previously described to functionally reduce transcription. This study represents the first sequence variant analysis of CHRNA7 in a sample of idiopathic autism. (c) 2015 Wiley Periodicals, Inc.
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2. Bernard PB, Castano AM, Beitzel CS, Carlson VB, Benke TA. {{Behavioral changes following a single episode of early-life seizures support the latent development of an autistic phenotype}}. {Epilepsy Behav};2015 (Feb 3);44C:78-85.
We probed the developmental and behavioral consequences of a single episode of kainic acid-induced early-life seizures (KA-ELS) in the rat on postnatal day 7. Correlates of developmental trajectory were not altered, demonstrating that long-term consequences following KA-ELS are not initiated by secondary causes, such as malnourishment or alterations in maternal care. We report reduced marble burying in adult rats, suggestive of restricted interests, a trait common to experimental and clinical autism. We did not detect increased repetitive grooming during habituated cage behavior. However, we did detect reduced grooming in adult KA-ELS rats in the presence of an unfamiliar rat, supporting altered social anxiety following KA-ELS. Reanalysis of a social approach task further indicated abnormal social interactions. Taken together with previous physiological and behavioral data, these data support the hypothesis that KA-ELS lead to a latent autistic phenotype in adult rats not attributable to other early alterations in development.
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3. Channell MM, Phillips BA, Loveall SJ, Conners FA, Bussanich PM, Klinger LG. {{Patterns of autism spectrum symptomatology in individuals with Down syndrome without comorbid autism spectrum disorder}}. {J Neurodev Disord};2015;7(1):5.
BACKGROUND: Prevalence estimates of autism spectrum disorder (ASD) in Down syndrome (DS) are highly varied. This variation is partly due to the difficulty of screening for and diagnosing comorbid ASD in individuals with a syndrome that carries its own set of social communicative and behavioral difficulties that are not well documented. The aim of this study was to identify the typical range of social communicative impairments observed in children, adolescents, and young adults with DS who do not have comorbid ASD. METHODS: We examined patterns of scores from the five subscales of the Social Responsiveness Scale (SRS) in 46 individuals with DS (ages 10-21 years) without comorbid ASD relative to the published normative sample. We also explored the correlations between SRS symptomatology and age, nonverbal cognition, and receptive language. RESULTS: SRS scores were elevated (i.e., more ASD symptoms endorsed), with mean scores falling into the clinically significant range. Analysis by subscale revealed a specific pattern, with Autistic Mannerisms and Social Cognition scores significantly more elevated than Social Communication scores, which were significantly more elevated than Social Awareness and Social Motivation scores. Correlations between SRS scores and the other measures varied by subscale. CONCLUSIONS: General elevated ASD symptomatology on the SRS indicates the need for developing population-based norms specific to DS. The pattern of scores across subscales should inform clinicians of the typical range of behaviors observed in DS so that individuals with atypical patterns of behavior can be more easily identified and considered for a full ASD evaluation.
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4. Gammer I, Bedford R, Elsabbagh M, Garwood H, Pasco G, Tucker L, Volein A, Johnson MH, Charman T. {{Behavioural markers for autism in infancy: Scores on the Autism Observational Scale for Infants in a prospective study of at-risk siblings}}. {Infant Behav Dev};2015 (Feb 2);38C:107-115.
We investigated early behavioural markers of autism spectrum disorder (ASD) using the Autism Observational Scale for Infants (AOSI) in a prospective familial high-risk (HR) sample of infant siblings (N=54) and low-risk (LR) controls (N=50). The AOSI was completed at 7 and 14 month infant visits and children were seen again at age 24 and 36 months. Diagnostic outcome of ASD (HR-ASD) versus no ASD (HR-No ASD) was determined for the HR sample at the latter timepoint. The HR group scored higher than the LR group at 7 months and marginally but non-significantly higher than the LR group at 14 months, although these differences did not remain when verbal and nonverbal developmental level were covaried. The HR-ASD outcome group had higher AOSI scores than the LR group at 14 months but not 7 months, even when developmental level was taken into account. The HR-No ASD outcome group had scores intermediate between the HR-ASD and LR groups. At both timepoints a few individual items were higher in the HR-ASD and HR-No ASD outcome groups compared to the LR group and these included both social (e.g. orienting to name) and non-social (e.g. visual tracking) behaviours. AOSI scores at 14 months but not at 7 months were moderately correlated with later scores on the autism diagnostic observation schedule (ADOS) suggesting continuity of autistic-like behavioural atypicality but only from the second and not first year of life. The scores of HR siblings who did not go on to have ASD were intermediate between the HR-ASD outcome and LR groups, consistent with the notion of a broader autism phenotype.
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5. Koch SV, Larsen JT, Mouridsen SE, Bentz M, Petersen L, Bulik C, Mortensen PB, Plessen KJ. {{Autism spectrum disorder in individuals with anorexia nervosa and in their first- and second-degree relatives: Danish nationwide register-based cohort-study}}. {Br J Psychiatry};2015 (Feb 5)
Background Clinical and population-based studies report increased prevalence of autism spectrum disorders (ASD) in individuals with anorexia nervosa and in their relatives. No nationwide study has yet been published on co-occurrence of these disorders. Aims To investigate comorbidity of ASD in individuals with anorexia nervosa, and aggregation of ASD and anorexia nervosa in their relatives. Method In Danish registers we identified all individuals born in 1981-2008, their parents, and full and half siblings, and linked them to data on hospital admissions for psychiatric disorders. Results Risk of comorbidity of ASD in probands with anorexia nervosa and aggregation of ASD in families of anorexia nervosa probands were increased. However, the risk of comorbid and familial ASD did not differ significantly from comorbid and familial major depression or any psychiatric disorder in anorexia nervosa probands. Conclusions We confirm aggregation of ASD in probands with anorexia nervosa and in their relatives; however, the relationship between anorexia nervosa and ASD appears to be non-specific.
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6. Pan Y, Chen J, Guo H, Ou J, Peng Y, Liu Q, Shen Y, Shi L, Liu Y, Xiong Z, Zhu T, Luo S, Hu Z, Zhao J, Xia K. {{Association of genetic variants of GRIN2B with autism}}. {Sci Rep};2015;5:8296.
Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 x 10(-4)). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 x 10(-6)). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 x 10(-3)) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk.
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7. Shimamoto C, Ohnishi T, Maekawa M, Watanabe A, Ohba H, Arai R, Iwayama Y, Hisano Y, Toyota T, Toyoshima M, Suzuki K, Shirayama Y, Nakamura K, Mori N, Owada Y, Kobayashi T, Yoshikawa T. {{Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies}}. {Hum Mol Genet};2015 (Feb 5)
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8. Wass SV, Jones EJ, Gliga T, Smith TJ, Charman T, Johnson MH. {{Shorter spontaneous fixation durations in infants with later emerging autism}}. {Sci Rep};2015;5:8284.
Little is known about how spontaneous attentional deployment differs on a millisecond-level scale in the early development of autism spectrum disorders (ASD). We measured fine-grained eye movement patterns in 6-to 9-month-old infants at high or low familial risk (HR/LR) of ASD while they viewed static images. We observed shorter fixation durations (i.e. the time interval between saccades) in HR than LR infants. Preliminary analyses indicate that these results were replicated in a second cohort of infants. Fixation durations were shortest in those infants who went on to receive an ASD diagnosis at 36 months. While these findings demonstrate early-developing atypicality in fine-grained measures of attentional deployment early in the etiology of ASD, the specificity of these effects to ASD remains to be determined.
