China
Africa
Explore chapters and articles related to this topic
Pathophysiology of hyperpigmentation
Published in Dimitris Rigopoulos, Alexander C. Katoulis, Hyperpigmentation, 2017
Shalini B. Reddy, Neelam A. Vashi
More than 150 genetic alleles are involved in coding for skin pigmentation and its related pathways.27 Hyperpigmented lesions in dyschromatosis symmetrica hereditaria (reticulate acropigmentation of Dohi), incontinentia pigmenti, linear and whorled nevoid hypermelanosis, and neurofibromatosis type I are due to gene defects affecting early melanocyte development and function. The reticular hyperpigmentation seen in Dowling–Degos syndrome and Naegeli–Franceschetti–Jadassohn syndrome is due to defects in keratin genes, which are involved in cell structure and metabolism. The lentigines of multiple lentigines syndrome and Peutz–Jeghers syndrome are a result of dysregulation of the Ras pathway. The hyperpigmentation of dyskeratosis congenita and xeroderma pigmentosum is due to gene defects involved in DNA repair.
Novel and emerging treatments for Aicardi-Goutières syndrome
Published in Expert Review of Clinical Immunology, 2020
Davide Tonduti, Elisa Fazzi, Raffaele Badolato, Simona Orcesi
In recent times, the identification of the causative genes of the syndrome and the advent of next-generation sequencing methods have resulted in a significant broadening of the phenotype associated to AGS-genes. Mild presentations have been reported as also patients fulfilling only partially the classic diagnostic criteria. It has also become clear that AGS genes can be associated to clinical phenotypes different from AGS such as Bilateral Striatal Degeneration, Cerebral vasculitis, Familial Chilblain Lupus, Systemic Lupus Erythematosous, Singleton Merten Syndrome, Spastic Paraplegia, Dyschromatosis Symmetrica Hereditaria, Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). At the same time the identification of the molecular basis of the disease leads to clarify many aspects of the pathogenesis of AGS, making it possible to propose new therapeutic strategies that are now rapidly becoming real.
RNA A-to-I editing, environmental exposure, and human diseases
Published in Critical Reviews in Toxicology, 2021
Various human diseases are associated with RNA A-to-I editing, which has been well-documented by enhancing A-to-I editing enzyme activities during diseases. Several comprehensive reviews on RNA A-to-I editing-diseases interaction have been published (Uchida and Jones 2018; Christofi and Zaravinos 2019; Dorn et al. 2019). Accumulating evidence indicates the association between RNA editing and neurodegenerative disorders, such as Alzheimer, Parkinson, and amyotrophic lateral sclerosis (ALS) (Krestel and Meier 2018). For example, in a study, editing defect in the GluR2 subunit of glutamate AMPA receptors transcripts have been observed in ALS patients. Such editing resulted in recoding the amino acid sequence affecting the function of the glutamate receptors (Kawahara et al. 2004). Although there are limited data regarding cardiovascular diseases, few studies presented the role of RNA editing on cardiovascular diseases. In a human study, RNA editing in pediatric patients with cyanotic congenital heart disease (CHD) was compared with acyanotic children’s results, and the author reported higher rates of RNA A-to-I editing in CHD. The authors suggested the possible role of RNA editing on CHD's cellular and metabolic pathways (Borik et al. 2011). In another study, Stellos et al. (2016) reported the role of RNA editing in human atherosclerotic vascular diseases. Specifically, the authors showed that transcripts of cathepsin S, linked with angiogenesis and atherosclerosis, were edited in human endothelial cells (Stellos et al. 2016). As mentioned before, RNA editing affected the function of miRNA. RNA A-to-I editing of miRNA-487b induced switching of target site selection after Ischemia and overexpression of edited miRNA-487b can stimulate angiogenesis (van der Kwast et al. 2018). Aicardi-Goutières syndrome (AGS) is an autoimmune disorder (Aicardi and Goutieres 1984) which has been associated with RNA edition. In the study, it was evidenced that mutations in ADAR caused AGC (Rice et al. 2012). Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant inheritance. It was reported different types of mutations in ADAR genes in patients with DSH (Liu et al. 2004). Systemic lupus erythematosus (SLE) is an chronic autoimmune disorder (Orlowski et al. 2008). The expression of RNA A-to-I editing modifying genes, such as ADAR1 and ADAR2 measure in blood cells, was elevated in SLE patients (Crow and Wohlgemuth 2003; Laxminarayana et al. 2007). Hypo-editing of RNA A-to-I editing was associated with upregulation of PDE8A1 gene in SLE patients (Orlowski et al. 2008). Different distribution of RNA editing sites has been reported in schizophrenia patients. It was reported that RNA editing sites was less in AMPA-type glutamate receptors genes and proteins related to post-synaptic density. On the other hand, hyper-edition was observed in translation initiation machinery genes. Overall, the RNA editing event has been reported in schizophrenia and in schizophrenia neuropathology (Breen et al. 2019).