Rare diseases (Austin, Tex.)最新文献_第5页

The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I). 遗传背景对K-Ras(V14I)诱导的Noonan综合征表型的影响

Rare diseases (Austin, Tex.) Pub Date : 2015-05-22 eCollection Date: 2015-01-01 DOI: 10.1080/21675511.2015.1045169

Isabel Hernández-Porras, Beatriz Jiménez-Catalán, Alberto J Schuhmacher, Carmen Guerra

引用次数: 12

Crosstalk between 2 organelles: Lysosomal storage of heparan sulfate causes mitochondrial defects and neuronal death in mucopolysaccharidosis III type C. 两细胞器间的串扰:溶酶体中硫酸肝素的储存导致III型粘多糖病的线粒体缺陷和神经元死亡。

Rare diseases (Austin, Tex.) Pub Date : 2015-05-21 eCollection Date: 2015-01-01 DOI: 10.1080/21675511.2015.1049793

Alexey V Pshezhetsky

{"title":"Crosstalk between 2 organelles: Lysosomal storage of heparan sulfate causes mitochondrial defects and neuronal death in mucopolysaccharidosis III type C.","authors":"Alexey V Pshezhetsky","doi":"10.1080/21675511.2015.1049793","DOIUrl":"https://doi.org/10.1080/21675511.2015.1049793","url":null,"abstract":"More than 30% of all lysosomal diseases are mucopolysaccharidoses, disorders affecting the enzymes needed for the stepwise degradation of glycosaminoglycans (mucopolysaccharides). Mucopolysaccharidosis type IIIC (MPS IIIC) is a severe neurologic disease caused by genetic deficiency of heparan sulfate acetyl-CoA: α-glucosaminide N-acetyltransferase (HGSNAT). Through our studies, we have cloned the gene, identified molecular defects in MPS IIIC patients and most recently completed phenotypic characterization of the first animal model of the disease, a mouse with a germline inactivation of the Hgsnat gene.(1) The obtained data have led us to propose that Hgsnat deficiency and lysosomal accumulation of heparan sulfate in microglial cells followed by their activation and cytokine release result in mitochondrial dysfunction in the neurons causing their death which explains why MPS IIIC manifests primarily as a neurodegenerative disease. The goal of this addendum is to summarize data yielding new insights into the mechanism of MPS IIIC and promising novel therapeutic solutions for this and similar disorders. ","PeriodicalId":74639,"journal":{"name":"Rare diseases (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21675511.2015.1049793","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34081322","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}

引用次数: 25

Corrigendum. 勘误表。

Rare diseases (Austin, Tex.) Pub Date : 2015-04-16 eCollection Date: 2015-01-01 DOI: 10.1080/21675511.2015.1037119

引用次数: 0

Ribosomopathies: Global process, tissue specific defects. 核糖体病:整体过程，组织特异性缺陷。

Rare diseases (Austin, Tex.) Pub Date : 2015-04-01 eCollection Date: 2015-01-01 DOI: 10.1080/21675511.2015.1025185

Pamela C Yelick, Paul A Trainor

{"title":"Ribosomopathies: Global process, tissue specific defects.","authors":"Pamela C Yelick, Paul A Trainor","doi":"10.1080/21675511.2015.1025185","DOIUrl":"https://doi.org/10.1080/21675511.2015.1025185","url":null,"abstract":"Disruptions in ribosomal biogenesis would be expected to have global and in fact lethal effects on a developing organism. However, mutations in ribosomal protein genes have been shown in to exhibit tissue specific defects. This seemingly contradictory finding - that globally expressed genes thought to play fundamental housekeeping functions can in fact exhibit tissue and cell type specific functions - provides new insight into roles for ribosomes, the protein translational machinery of the cell, in regulating normal development and disease. Furthermore it illustrates the surprisingly dynamic nature of processes regulating cell type specific protein translation. In this review, we discuss our current knowledge of a variety of ribosomal protein mutations associated with human disease, and models to better understand the molecular mechanisms associated with each. We use specific examples to emphasize both the similarities and differences between the effects of various human ribosomal protein mutations. Finally, we discuss areas of future study that are needed to further our understanding of the role of ribosome biogenesis in normal development, and possible approaches that can be used to treat debilitating ribosomopathy diseases. ","PeriodicalId":74639,"journal":{"name":"Rare diseases (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21675511.2015.1025185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34067318","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}

引用次数: 94

New insights into the pathophysiology of the tuberous sclerosis complex: Crosstalk of mTOR- and hippo-YAP pathways in cell growth. 结节性硬化症复合体病理生理学的新见解:细胞生长中mTOR-和hippo-YAP通路的串扰。

Rare diseases (Austin, Tex.) Pub Date : 2015-02-23 eCollection Date: 2015-01-01 DOI: 10.1080/21675511.2015.1016701

Patricia E Dill, Ning Liang, Mario Pende

引用次数: 5

The immune system in Duchenne muscular dystrophy: Friend or foe. 杜氏肌肉萎缩症的免疫系统：是敌是友

Rare diseases (Austin, Tex.) Pub Date : 2015-02-23 eCollection Date: 2015-01-01 DOI: 10.1080/21675511.2015.1010966

S Armando Villalta, Amy S Rosenberg, Jeffrey A Bluestone

{"title":"The immune system in Duchenne muscular dystrophy: Friend or foe.","authors":"S Armando Villalta, Amy S Rosenberg, Jeffrey A Bluestone","doi":"10.1080/21675511.2015.1010966","DOIUrl":"10.1080/21675511.2015.1010966","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutations in the X-linked dystrophin gene, resulting in reduced or absent protein production, subsequently leading to the structural instability of the dystroglycan complex (DGC), muscle degeneration, and early death in males. Thus, current treatments have been targeting the genetic defect either by bypassing the mutation through exon skipping or replacing the defective gene through gene therapy and stem cell approaches. However, what has been an underappreciated mediator of muscle pathology and, ultimately, of muscle degeneration and fibrotic replacement, is the prominent inflammatory response. Of potentially critical importance, however, is the fact that the elements mediating the inflammatory response also play an essential role in tissue repair. In this opinion piece, we highlight the detrimental and supportive immune parameters that occur as a consequence of the genetic disorder and discuss how changes to immunity can potentially ameliorate the disease intensity and be employed in conjunction with efforts to correct the genetic disorder. ","PeriodicalId":74639,"journal":{"name":"Rare diseases (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/14/krad-03-01-1010966.PMC4588155.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34269601","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}

引用次数: 0

Human iPS cell models of Jervell and Lange-Nielsen syndrome. Jervell综合征和Lange-Nielsen综合征的人类iPS细胞模型。

Rare diseases (Austin, Tex.) Pub Date : 2015-02-03 eCollection Date: 2015-01-01 DOI: 10.1080/21675511.2015.1012978

Milena Bellin, Boris Greber

引用次数: 6

Pompe disease: Shared and unshared features of lysosomal storage disorders 庞贝病:溶酶体贮积症的共有和非共有特征

Rare diseases (Austin, Tex.) Pub Date : 2015-01-01 DOI: 10.1080/21675511.2015.1068978

Jeong-A Lim, O. Kakhlon, Lishu Li, R. Myerowitz, N. Raben

{"title":"Pompe disease: Shared and unshared features of lysosomal storage disorders","authors":"Jeong-A Lim, O. Kakhlon, Lishu Li, R. Myerowitz, N. Raben","doi":"10.1080/21675511.2015.1068978","DOIUrl":"https://doi.org/10.1080/21675511.2015.1068978","url":null,"abstract":"Pompe disease, an inherited deficiency of lysosomal acid α-glucosidase (GAA), is a severe metabolic myopathy with a wide range of clinical manifestations. It is the first recognized lysosomal storage disorder and the first neuromuscular disorder for which a therapy (enzyme replacement) has been approved. As GAA is the only enzyme that hydrolyses glycogen to glucose in the acidic environment of the lysosome, its deficiency leads to glycogen accumulation within and concomitant enlargement of this organelle. Since the introduction of the therapy, the overall understanding of the disease has progressed significantly, but the pathophysiology of muscle damage is still not fully understood. The emerging complex picture of the pathological cascade involves disturbance of calcium homeostasis, mitochondrial abnormalities, dysfunctional autophagy, accumulation of toxic undegradable materials, and accelerated production of lipofuscin deposits that are unrelated to aging. The relationship of Pompe disease to other lysosomal storage disorders and potential therapeutic interventions for Pompe disease are discussed.","PeriodicalId":74639,"journal":{"name":"Rare diseases (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21675511.2015.1068978","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60423108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Developing methodology for the creation of clinical practice guidelines for rare diseases: A report from RARE-Bestpractices 制定罕见病临床实践指南的方法学:罕见最佳实践报告

Rare diseases (Austin, Tex.) Pub Date : 2015-01-01 DOI: 10.1080/21675511.2015.1058463

M. Pai, A. Iorio, J. Meerpohl, D. Taruscio, P. Laricchiuta, P. Mincarone, C. Morciano, C. Leo, S. Sabina, E. Akl, S. Treweek, B. Djulbegovic, H. Schunemann

{"title":"Developing methodology for the creation of clinical practice guidelines for rare diseases: A report from RARE-Bestpractices","authors":"M. Pai, A. Iorio, J. Meerpohl, D. Taruscio, P. Laricchiuta, P. Mincarone, C. Morciano, C. Leo, S. Sabina, E. Akl, S. Treweek, B. Djulbegovic, H. Schunemann","doi":"10.1080/21675511.2015.1058463","DOIUrl":"https://doi.org/10.1080/21675511.2015.1058463","url":null,"abstract":"Rare diseases are a global public health priority; they can cause significant morbidity and mortality, can gravely affect quality of life, and can confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by clinicians. Thus, clinical practice guidelines are potentially very helpful in supporting clinical decisions, health policy and resource allocation. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system is a structured and transparent approach to developing and presenting summaries of evidence, grading its quality, and then transparently interpreting the available evidence to make recommendations in health care. GRADE has been adopted widely. However, its use in creating guidelines for rare diseases – which are often plagued by a paucity of high quality evidence – has not yet been explored. RARE-Bestpractices is a project to create and populate a platform for sharing best practices for management of rare diseases. A major aim of this project is to ensure that European Union countries have the capacity to produce high quality clinical practice guidelines for rare diseases. On February 12, 2013 at the Istituto Superiore di Sanità, in Rome, Italy, the RARE-Bestpractices group held the first of a series of 2 workshops to discuss methodology for creating clinical practice guidelines, and explore issues specific to rare diseases. This paper summarizes key results of the first workshop, and explores how the current GRADE approach might (or might not) work for rare diseases. Avenues for future research are also identified.","PeriodicalId":74639,"journal":{"name":"Rare diseases (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21675511.2015.1058463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60422899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

FUS-regulated RNA metabolism and DNA damage repair: Implications for amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis. fus调节的RNA代谢和DNA损伤修复:肌萎缩侧索硬化和额颞叶痴呆发病机制的意义。

Rare diseases (Austin, Tex.) Pub Date : 2014-06-12 eCollection Date: 2014-01-01 DOI: 10.4161/rdis.29515

Yueqin Zhou, Songyan Liu, Arzu Oztürk, Geoffrey G Hicks

{"title":"FUS-regulated RNA metabolism and DNA damage repair: Implications for amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis.","authors":"Yueqin Zhou, Songyan Liu, Arzu Oztürk, Geoffrey G Hicks","doi":"10.4161/rdis.29515","DOIUrl":"https://doi.org/10.4161/rdis.29515","url":null,"abstract":"Cytoplasmic inclusion of RNA binding protein FUS/TLS in neurons and glial cells is a characteristic pathology of a subgroup of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dysregulation of RNA metabolism caused by FUS cytoplasmic inclusion emerges to be a key event in FUS-associated ALS/FTD pathogenesis. Our recent discovery of a FUS autoregulatory mechanism and its dysregulation in ALS-FUS mutants demonstrated that dysregulated alternative splicing can directly exacerbate the pathological FUS accumulation. We show here that FUS targets RNA for pre-mRNA alternative splicing and for the processing of long intron-containing transcripts, and that these targets are enriched for genes in neurogenesis and gene expression regulation. We also identify that FUS RNA targets are enriched for genes in the DNA damage response pathway. Together, the data support a model in which dysregulated RNA metabolism and DNA damage repair together may render neurons more vulnerable and accelerate neurodegeneration in ALS and FTD. ","PeriodicalId":74639,"journal":{"name":"Rare diseases (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/rdis.29515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32552462","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}

引用次数: 3