6 research outputs found
Pan-European initiatives for the study of the genetics of Gilles de la Tourette Syndrome
Pan-European initiatives for the study of the genetics of Gilles de la Tourette Syndrome
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De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis
We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk.
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•Recurrent de novo variants identify a new high-confidence TD risk gene: CELSR3•Genes involved in cell polarity are more likely to be disrupted by de novo variants•De novo sequence variants may carry more risk in simplex families, female probands•De novo CNVs occur 2 to 3 times more often in TD probands than in matched controls
Wang et al. expand their earlier exome-sequencing work in TD, adding 291 trios and conducting combined analyses suggesting de novo variants carry more risk in individuals with unaffected parents, establishing de novo structural variants as risk factors, identifying CELSR3 as a risk gene, and implicating cell polarity in pathogenesis
Diagnostics and Intervention in Developmental Dyscalculia: Current Issues and Novel Perspectives
Developmental dyscalculia is one of the most prevalent learning disorders observed in children. However, it has received much less research interest than, for instance, developmental dyslexia. Thus our knowledge about aetiology, aetiopathology and symptomatology of dyscalculia remains patchy; and empirically validated approaches on remediation and intervention are still scarce. In the current chapter we first discuss the theoretical underpinnings of developmental dyscalculia, paying particular attention to its still debated aetiology: Some authors suggest the heterogeneous symptoms of developmental dyscalculia to be caused by a single underlying deficit of the number sense, while others propose different deficits in basic numerical competencies as its determinants (as observed in adult acalculia). Second, the implications of this differentiation on dyscalculia diagnostics are discussed. In particular, we focus on the importance of cut off criteria, sample selection, and their influence on the epidemiology of developmental dyscalculia. In a third section, the issue of comorbidity and its estimation will be evaluated. And finally, existing intervention approaches are reviewed in light of their theoretical underpinnings and practical applications. We conclude that we are on a promising way to better understand, diagnose and treat brain-based dyscalculia with innovative novel methodology.publishe