China
Africa
Explore chapters and articles related to this topic
Neurology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Fenella Kirkham, Adnan Manzur, Stephanie Robb
Congenital myasthenic syndromes (CMS) are inherited (usually recessively except for slow channel syndromes). Mutations in at least 19 genes cause pre- and postsynaptic abnormalities. The commonest are postsynaptic disorders, including: AChR deficiency due to mutations in CHRNE, encoding the epsilon AChR subunit.CMS due to mutations in RAPSN.‘Limb girdle’ CMS due to mutations in DOK7.
Methylomic and transcriptomic predictors of one-month exposure to cortisol in healthy individuals
Published in Stress, 2021
Richard S. Lee, Peter P. Zandi, Yian Lin, Fayaz Seifuddin, Kelly S. Benke, Mary E. McCaul, Kendall Reitz, Gary S. Wand
Third, we interrogated more than 2.7 million CpGs (after QC of the 3.7 million CpGs possible) for the methylation analysis. The use of the next-generation sequencing platform enabled us to more than triple the number of CpGs currently available on human array platforms. Finally, we also observed that many of the CpGs and DEGs were associated with experimentally verified GC-response elements (GREs). Of the fifteen CpG and DEG predictors, ten were associated with genes that harbored ENCODE-verified GREs, which strengthens our finding that these predictors are linked to GC signaling. Of the ten CpGs and DEGs that were associated with GREs, four have been independently implicated in GC signaling. For instance, VPS8, or vacuolar protein sorting-associated protein 8 homolog, responds to prednisolone treatment in patients with polymyalgia rheumatica (Kreiner et al., 2017). Similarly, WDR60, or WD repeat-containing protein 60, is a DEX-regulated gene in B-cell precursor acute lymphoblastic leukemia (Bhadri et al., 2011). ISPD, or isoprenoid synthase domain-containing protein, is one of a growing number of genes that are dysregulated in muscular dystrophy and responds to GC therapy (Wu et al., 2016). Several studies have linked the cholinergic system and GC signaling, although it is unclear whether the CHRNE gene, which encodes the cholinergic receptor nicotinic epsilon subunit protein, is directly regulated by GCs (Bouzat & Barrantes, 1996; Kindler et al., 2000). We then asked whether the genomic coordinates of all P-value-significant (p < 0.005) DMRs overlapped with those of the ENCODE GREs, but we did not observe a significant enrichment of GREs more than expected by chance. Future studies will determine if the combination of biomarkers is useful in diagnosing and managing Cushing syndrome, monitoring stress levels, helping to titrate GC dosing in patients with adrenal insufficiency, and predicting future metabolic and neuropsychiatric disorders.