Project description:The sex chromosome-encoded RNA helicases DDX3X and DDX3Y play important roles in RNA metabolism. Heterozygous mutations of DDX3X frequently occur in cancers and neurodevelopmental disorders which have strong sex biases. However, how different DDX3X variants impair cellular function in sex specific genetic background is not understood. Herein, we found that DDX3X variants with significantly impaired ATPase activities demixed into the shells of unique hollow condensates, the dynamics of which were further differentiated by the RNA binding affinities of the different DDX3X variants. Proteomic and imaging studies revealed that DDX3X variant condensates sequestered wild-type DDX3X, DDX3Y, and other proteins important for various signaling pathways. Intriguingly, wild-type DDX3X improved the dynamics of heterogenous variant/wild-type hollow condensates more than DDX3Y. These results suggest that DDX3X variants with distinct enzymatic and condensation propensities may interact uniquely with wild-type DDX3X or DDX3Y to cause sex-specific cellular impacts.
Project description:This study includes the whole-genome screening of unbalanced chromosomal rearrangements (copy-number variants; CNV) in children with ID/DD, ASD and MCA. We identified a broad range of pathogenic/likely pathogenic CNVs as well as variants of unclear significance and likely benign variants. Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics through the identification of genetic cause of ID/DD in the high proportion of affected children.
Project description:This study includes the whole-genome screening of unbalanced chromosomal rearrangements (copy-number variants; CNV) in children with ID/DD, ASD and MCA. We identified a broad range of pathogenic/likely pathogenic CNVs as well as variants of unclear significance and likely benign variants. Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics through the identification of genetic cause of ID/DD in the high proportion of affected children.
Project description:This study includes the whole-genome screening of unbalanced chromosomal rearrangements (copy-number variants; CNV) in children with ID/DD, ASD and MCA. We identified a broad range of pathogenic/likely pathogenic CNVs as well as variants of unclear significance and likely benign variants. Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics through the identification of genetic cause of ID/DD in the high proportion of affected children.
Project description:This study includes the whole-genome screening of unbalanced chromosomal rearrangements (copy-number variants; CNV) in children with ID/DD, ASD and MCA. We identified a broad range of pathogenic/likely pathogenic CNVs as well as variants of unclear significance and likely benign variants. Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics through the identification of genetic cause of ID/DD in the high proportion of affected children.
Project description:This study includes the whole-genome screening of unbalanced chromosomal rearrangements (copy-number variants; CNV) in children with ID/DD, ASD and MCA. We identified a broad range of pathogenic/likely pathogenic CNVs as well as variants of unclear significance and likely benign variants. Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics through the identification of genetic cause of ID/DD in the high proportion of affected children.
Project description:This study includes the whole-genome screening of unbalanced chromosomal rearrangements (copy-number variants; CNV) in children with ID/DD, ASD and MCA. We identified a broad range of pathogenic/likely pathogenic CNVs as well as variants of unclear significance and likely benign variants. Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics through the identification of genetic cause of ID/DD in the high proportion of affected children.
Project description:This study includes the whole-genome screening of unbalanced chromosomal rearrangements (copy-number variants; CNV) in children with ID/DD, ASD and MCA. We identified a broad range of pathogenic/likely pathogenic CNVs as well as variants of unclear significance and likely benign variants. Our results confirm the benefit of array-CGH in the current clinical genetic diagnostics through the identification of genetic cause of ID/DD in the high proportion of affected children.
Project description:Rasmussen encephalitis is a unilateral encephalitis characterized by treatment-resistant epilepsy and progressive cognitive and motor decline. MRI reveals inflammation and neuropathology reveals reactive astrocytes, microglial activation, microglial nodules, T cell infiltration, and neuronal loss.
Despite the abundant evidence of altered signaling pathways in Rasmussen brain tissue and associated genetic variants, the mechanisms remain poorly understood, and it is uncertain which are a part or result of the underlying cause
In Rasmussen brain tissue, we identified by RNAseq altered immune signaling pathways, immune cell type annotation enrichment, and by whole exome sequencing HLA variants more common to Rasmussen. These findings demonstrate immune cell infiltration associated with innate and adaptive immune responses, as well as HLA variants that may increase vulnerability to RE.
