Toward robust clinical genome interpretation: Developing a consistent terminology to characterize Mendelian disease-gene relationships-allelic requirement, inheritance modes, and disease mechanisms.

Purpose: The terminology used for gene-disease curation and variant annotation to describe inheritance, allelic requirement, and both sequence and functional consequences of a variant is currently not standardized. There is considerable discrepancy in the literature and across clinical variant reporting in the derivation and application of terms. Here, we standardize the terminology for the characterization of disease-gene relationships to facilitate harmonized global curation and to support variant classification within the ACMG/AMP framework.

Variability and concordance of sulcal patterns in the orbitofrontal cortex: A twin study.

Sulcogyral patterns have been identified in the orbitofrontal cortex (OFC) based on the continuity of the medial and lateral orbital sulci. Pattern types are named according to their frequency in the population, with Type I present in ∼60%, Type II in ∼25%, Type III in ∼10%, and Type IV in ∼5%. Previous work has demonstrated that psychiatric conditions with high estimated heritability (e.

Pediatric Head CT: Automated Quantitative Analysis with Quantile Regression.

Background And Purpose: Together with quantile regression methods, such a model would have the potential for clinical utility through automated quantitative comparison of individual cases relative to their age and gender-matched peer group. Our aim was to demonstrate the automated processing of digital clinical head CT data in the development of a clinically useful model of age-related changes of the brain in the first 2 decades of life.

Materials And Methods: A total of 415 (209 female) consecutive, clinical head CTs with radiographically normal findings from patients from birth through 20 years of age were retrospectively selected and subjected to automated segmentation.

Insufficient Evidence for "Autism-Specific" Genes.

Despite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively "autism-specific" genes, efforts which focus on rare variants of large effect size that are thought to account for the observed phenotypes. We present a divergent interpretation of published evidence; discuss practical and theoretical issues related to studying the relationships between rare, large-effect deleterious variants and neurodevelopmental phenotypes; and describe potential future directions of this research.

The Broader Autism Phenotype and Visual Perception in Children.

Atypical visual perception has increasingly been described in individuals with autism spectrum disorders (ASD) and linked to quantitative, autism-like features that are present in children and adults without ASD. We investigated whether individual differences in visual processing skills were related to quantitative measures of autism traits in a pediatric sample with a range of clinical features. Visual processing was comprehensively characterized using the test of visual perceptual skills (TVPS), a standardized test of visual perception with seven subtests that capture a range of visual processing abilities.

Pupil adaptation corresponds to quantitative measures of autism traits in children.

The pupil is known to reflect a range of psychological and physiological variables, including cognitive effort, arousal, attention, and even learning. Within autism spectrum disorder (ASD), some work has used pupil physiology to successfully classify patients with or without autism. As we have come to understand the heterogeneity of ASD and other neurodevelopmental disorders, the relationship between quantitative traits and physiological markers has become increasingly more important, as this may lead us closer to the underlying biological basis for atypical responses and behaviors.

Brief Report: Autism-like Traits are Associated With Enhanced Ability to Disembed Visual Forms.

Atypical visual perceptual skills are thought to underlie unusual visual attention in autism spectrum disorders. We assessed whether individual differences in visual processing skills scaled with quantitative traits associated with the broader autism phenotype (BAP). Visual perception was assessed using the Figure-ground subtest of the Test of visual perceptual skills-3rd Edition (TVPS).

Brief Report: Cognitive Control of Social and Nonsocial Visual Attention in Autism.

Prosaccade and antisaccade errors in the context of social and nonsocial stimuli were investigated in youth with autism spectrum disorder (ASD; n = 19) a matched control sample (n = 19), and a small sample of youth with obsessive compulsive disorder (n = 9). Groups did not differ in error rates in the prosaccade condition for any stimulus category. In the antisaccade condition, the ASD group demonstrated more errors than the control group for nonsocial stimuli related to circumscribed interests, but not for other nonsocial stimuli or for social stimuli.

Multidimensional frequency domain analysis of full-volume fMRI reveals significant effects of age, gender, and mental illness on the spatiotemporal organization of resting-state brain activity.

Clinical research employing functional magnetic resonance imaging (fMRI) is often conducted within the connectionist paradigm, focusing on patterns of connectivity between voxels, regions of interest (ROIs) or spatially distributed functional networks. Connectivity-based analyses are concerned with pairwise correlations of the temporal activation associated with restrictions of the whole-brain hemodynamic signal to locations of a priori interest. There is a more abstract question however that such spatially granular correlation-based approaches do not elucidate: Are the broad spatiotemporal organizing principles of brains in certain populations distinguishable from those of others? Global patterns (in space and time) of hemodynamic activation are rarely scrutinized for features that might characterize complex psychiatric conditions, aging effects or gender-among other variables of potential interest to researchers.

Neural Mechanisms of Emotion Regulation in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by high rates of comorbid internalizing and externalizing disorders. One mechanistic account of these comorbidities is that ASD is characterized by impaired emotion regulation (ER) that results in deficits modulating emotional responses. We assessed neural activation during cognitive reappraisal of faces in high functioning adults with ASD.

AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission.

Background: The presence of AGG interruptions in the CGG repeat locus of the fragile X mental retardation 1 (FMR1) gene decreases the instability of the allele during transmission from parent to child, and decreases the risk of expansion of a premutation allele to a full mutation allele (the predominant cause of fragile X syndrome) during maternal transmission.

Methods: To strengthen recent findings on the utility of AGG interruptions in predicting instability or expansion to a full mutation of FMR1 CGG repeat alleles, we assessed the outcomes of 108 intermediate (also named gray zone) and 710 premutation alleles that were transmitted from parent to child, and collected from four international clinical sites. We have used the results to revise our initial model that predicted the risk of a maternal premutation allele expanding to a full mutation during transmission and to test the effect of AGG interruptions on the magnitude of expanded allele instability of intermediate or premutation alleles that did not expand to a full mutation.