Mouse Models of 22q11.2-Associated Autism Spectrum Disorder.
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ABSTRACT:
SUBMITTER: Hiroi N
PROVIDER: S-EPMC4118685 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Mouse Models of 22q11.2-Associated Autism Spectrum Disorder.
Hiroi Noboru N Hiramoto Takeshi T Harper Kathryn M KM Suzuki Go G Boku Shuken S
Autism-open access 20120101
Copy number variation (CNV) of human chromosome 22q11.2 is associated with an elevated rate of autism spectrum disorder (ASD) and represents one of syndromic ASDs with rare genetic variants. However, the precise genetic basis of this association remains unclear due to its relatively large hemizygous and duplication region, including more than 30 genes. Previous studies using genetic mouse models suggested that although not all 22q11.2 genes contribute to ASD symptomatology, more than one 22q11.2 ...[more]
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Project description:22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition associated with a high prevalence of neuropsychiatric conditions that include autism spectrum disorder (ASD). While evidence suggests that clinical phenotypes represent distinct neurodevelopmental outcomes, it remains unknown whether this translates to the level of neurobiology. To fractionate the 22q11.2DS phenotype on the level of neuroanatomy, we examined differences in vertex-wise estimates of cortical volume, surface area, and cortical thickness between 1) individuals with 22q11.2DS (n = 62) and neurotypical controls (n = 57) and 2) 22q11.2DS individuals with ASD symptomatology (n = 30) and those without (n = 25). We firstly observed significant differences in surface anatomy between 22q11.2DS individuals and controls for all 3 neuroanatomical features, predominantly in parietotemporal regions, cingulate and dorsolateral prefrontal cortices. We also established that 22q11.2DS individuals with ASD symptomatology were neuroanatomically distinct from 22q11.2DS individuals without ASD symptoms, particularly in brain regions that have previously been linked to ASD (e.g., dorsolateral prefrontal cortices and the entorhinal cortex). Our findings indicate that different clinical 22q11.2DS phenotypes, including those with ASD symptomatology, may represent different neurobiological subgroups. The spatially distributed patterns of neuroanatomical differences associated with ASD symptomatology in 22q11.2DS may thus provide useful information for patient stratification and the prediction of clinical outcomes.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-07 | E-GEOD-61492 | biostudies-arrayexpress
Project description:Background and aimChildren with Developmental Language Disorder (DLD) are at an increased risk to develop behaviors associated with Autism Spectrum Disorder (ASD). The relationship between early language difficulties and the occurrence of ASD-related behaviors in DLD is poorly understood. One factor that may hinder progress in understanding this relationship is the etiological heterogeneity of DLD. We therefore study this relationship in an etiologically homogeneous group of children, who share phenotypic characteristics with children with DLD: children with the 22q11.2 Deletion Syndrome (22q11DS). We compare children with 22q11DS, to children with DLD and age-matched typically developing children (TD).Method44 children with 22q11DS, 65 children with DLD and 81 TD children, between 3.0-6.5 years old, participated in a longitudinal cohort study that included a baseline measure and a follow-up measure with a 1-year interval. A parental questionnaire (SRS-2) was used to measure the incidence of behaviors in two key behavioral domains associated with ASD: Social Communication and Interaction and Restricted Repetitive Behaviors and Interests. At baseline, we assessed children's expressive and receptive language abilities as well as their intellectual functioning with standardized tests. We compared the distribution of ASD-related behaviors between the three groups. We used regression analyses to investigate whether language abilities at baseline predict ASD-related behavior at follow-up, accounting for ASD-related behavior at baseline, demographic variables and intellectual functioning.ResultsBoth the children with 22q11DS and the children with DLD displayed significantly more ASD-related behaviors than the TD children. Over 30% of children in both clinical groups had scores exceeding the subclinical threshold for ASD in both behavioral domains. Both in 22q11DS and DLD, baseline receptive language scores were negatively correlated with ASD-related behaviors 1 year later, when controlling for baseline SRS-scores. However, this association was statistically significant only in children with 22q11DS, even when controlled for IQ-scores, and it was significantly stronger as than in the TD group. The strength of the association did not differ significantly between 22q11DS and DLD.ConclusionBoth children with 22q11DS and children with DLD present with elevated rates of ASD-related behaviors at a preschool-age. Only in children with 22q11DS we observed that weaker receptive language skills were related to increased behavioral problems in the domain of social communication and interaction one year later.ImplicationsOur findings indicate that relations between early language impairment and other behavioral phenotypes may be more feasible to detect in a subgroup of children with a homogeneous etiology, than in a group of children with a heterogeneous etiology (such as children with DLD). Our results in 22q11DS reveal that receptive language is especially important in predicting the occurrence of ASD-related behaviors. Future research is needed to determine to what extent receptive language predicts the occurrence of ASD-related behaviors in children with DLD, especially among those children with DLD with the weakest receptive language. Clinically, screening for ASD-related behaviors in children with developmental language difficulties is recommended from a young age, especially among children with receptive language difficulties.
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