Journal of genetic disorders & genetic reports最新文献

{"title":"Clinical and Molecular Assessment in a Female with Fragile X Syndrome and Tuberous Sclerosis.","authors":"Carolyn M Yrigollen, Laura Pacini, Veronica Nobile, Reymundo Lozano, Randi J Hagerman, Claudia Bagni, Flora Tassone","doi":"10.4172/2327-5790.1000139","DOIUrl":"10.4172/2327-5790.1000139","url":null,"abstract":"<p><strong>Objective: </strong>Fragile X syndrome (FXS) and tuberous sclerosis (TSC) are genetic disorders that result in intellectual disability and an increased prevalence of autism spectrum disorders (ASD). While the clinical presentation of each disorder is distinct, the molecular causes are linked to a disruption in the mTORC1 (mammalian Target of Rapamycin Complex 1) and ERK1/2 (Extracellular signal-Regulated Kinase) signaling pathways.</p><p><strong>Methods: </strong>We assessed the clinical and molecular characteristics of an individual seen at the UC Davis MIND Institute with a diagnosis of FXS and TSC. Clinical evaluation of physical, behavioral, and cognitive impairments were performed. Additionally, total and phosphorylated proteins along the mTORC1 and ERK1/2 pathways were measured in primary fibroblast cell lines from the proband.</p><p><strong>Results: </strong>In this case the phenotypic effects that result in a human with both FXS and TSC are shown to be severe. Changes in mTORC1 and ERK1/2 signaling proteins and global protein synthesis were not found to be noticeably different between four cohorts (typically developing, <i>FMR1</i> full mutation, <i>FMR1</i> full mutation and <i>TSC1</i> loss of function mutation, and <i>TSC1</i> loss of function mutation); however cohort sizes prevented stringent comparisons.</p><p><strong>Conclusion: </strong>It has previously been suggested that disruption of the mTORC1 pathway was reciprocal in TSC and FXS double knock-out mouse models so that the regulation of these pathways were more similar to wild-type mice compared to mice harboring a <i>Fmr1^-/y</i> or <i>Tsc2^-/+</i> mutation alone. However, in this first reported case of a human with a diagnosis of both FXS and TSC, substantial clinical impairments, as a result of these two disorders were observed. Differences in the mTORC and ERK1/2 pathways were not clearly established when compared between individuals with either disorder, or both.</p>","PeriodicalId":90219,"journal":{"name":"Journal of genetic disorders & genetic reports","volume":"5 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319728/pdf/nihms837880.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34760100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Genomic Evidence for Oxidative Stress in Experimental Radiation Nephropathy.","authors":"Eric P Cohen,&nbsp;Marek Lenarczyk,&nbsp;Brian L Fish,&nbsp;Shuang Jia,&nbsp;Martin J Hessner,&nbsp;John E Moulder","doi":"10.4172/2327-5790.1000101","DOIUrl":"https://doi.org/10.4172/2327-5790.1000101","url":null,"abstract":"<p><strong>Background: </strong>Chronic persistent oxidative stress has been proposed as a mechanism for late radiation injury to normal tissue. Using biochemical, histological, and pharmacological techniques, we have not been able to confirm this hypothesis for late renal radiation injury. Gene expression may be more revealing, especially since the initial effects of radiation are to damage DNA.</p><p><strong>Methods: </strong>Gene array studies were done using kidney tissue from irradiated rats, with particular attention to genes pertinent to oxidative stress. The time points were from 1 to 49 days after irradiation. Cellular RNA and mitochondrial DNA were isolated, for gene expression analysis and common deletion testing, respectively.</p><p><strong>Results: </strong>For the gene expression studies, and from over 30,000 transcripts, only nine related to oxidative stress had 1.4 fold or greater changes in expression. Mitochondrial DNA showed no changes in the common deletion.</p><p><strong>Conclusion: </strong>These studies do not support the hypothesis of chronic oxidative stress as a mechanism for radiation nephropathy.</p>","PeriodicalId":90219,"journal":{"name":"Journal of genetic disorders & genetic reports","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013680/pdf/nihms475537.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32334573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}