1,721,020 research outputs found
The medical genetics of dystrophinopathies: Molecular genetic diagnosis and its impact on clinical practice
No full textA large variety of mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies, diseases affecting predominantly the striated muscles (skeletal and cardiac). Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein is encoded by a huge gene located on the X chromosome and the understanding of its complex genomic architecture has unraveled general key functions in gene expression regulation. Dystrophin also exists as a number of other tissue specific isoforms, some exclusively or predominantly expressed in the brain and/or in other tissues. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has also provided insights regarding several regulatory mechanisms governing the gene expression profile. This review focuses on the current understanding of the dystrophin mutations heterogeneity, genotype-phenotype correlations, as well as interpretation of the functional significance of mutations that often require non routine genetic studies. It also explores the impact of genetic diagnosis on clinical definition and on the discovery of biomarkers and personalized therapies.Our aim is to offer an overview of the medical genetic approach on the dystrophin gene and dystrophinopathies with implications for clinical practice and therapeutic perspectives. © 2012 Elsevier B.V
Biomarkers in rare neuromuscular diseases
No full textNeuromuscular diseases (NMDs) comprise a range of rare disorders that include both hereditary peripheral neuropathies and myopathies. The heterogeneity and rarity of neuromuscular disorders are challenges for researchers seeking to develop effective diagnosis and treatment strategies. In particular, clinical trials of new therapies are made more difficult due to lack of reliable and monitorable clinical outcome measures. Biomarkers could be a way to speed up research in this field, shedding light on the pathophysiological mechanisms behind such diseases and providing invaluable tools for monitoring their progression, prognosis and response to drug treatment. Furthermore, biomarkers could represent a surrogate endpoint for clinical trials, enabling better stratification of patient cohorts through more accurate diagnosis and prognosis prediction.
This review summarizes the types, applications, characteristics and best strategies for biomarker discovery to date
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
A missense mutation in the coiled-coil domain of the KIF5A gene and late-onset hereditary spastic paraplegia
No full textTo our knowledge, up to now, only 2 mutations in the KIF5A gene, a member of the kinesin superfamily, have been identified as the molecular cause of early-onset autosomal dominant hereditary spastic paraparesis (ADHSP).
To assess the genetic defect in a family with late-onset ADHSP.
Only the proband agreed to undergo complete neurological testing and mutational analysis. The proband was screened for mutations in the spastin, atlastin, NIPA1, and KIF5A genes, either by denaturing high-performance liquid chromatography or sequence analysis.
The history of the family was consistent with ADHSP characterized by late onset of the disease. Mutational analysis results were negative for the spastin, atlastin, and NIPA1 genes but identified a missense mutation (c.1082C>T) in the coiled-coil coding region of the KIF5A gene.
This finding enlarges the phenotypic spectrum of ADHSP linked to KIF5A and enhances the role of that gene in the epidemiology of this disease. We propose that the KIF5A gene should be routinely analyzed in patients with hereditary spastic paraplegia negative for spastin and atlastin mutations
Sguardi sul futuro. Psicologia della comunicazione della diagnosi di Malattia di Huntington nella consulenza genetica.
No full textLa consulenza genetica è un lavoro multidisciplinare in cui il ruolo dello psicologo clinico comprende una valutazione degli aspetti comunicativi (scambio di informazioni significative) ed un intervento finalizzato a favorire un adattamento positivo ai possibili esiti della comunicazione di una futura malattia di sicura insorgenza nei soggetti che abbiano ereditato il tratto genomico patologico. Il caso clinico presentato, soggetto con diagnosi di Disturbo Bipolare sottoposto a consulenza genetica e diagnosi prenatale nella partner gravida motivate dal possibile rischio di ricorrenza di Malattia di Huntington e di Fibrosi Cistica, delinea la complessità e le finalità della consulenza genetica nelle sue più importanti implicazioni psicologiche
NMD CHIP: Un Progetto Europeo per la diagnosi delle patologie neuromuscolari
No full textLe malattie neuromuscolari sono un ampio gruppo di patologie ereditarie caratterizzate da eterogeneità genetica e allelica. La
diagnosi molecolare è talora un processo lungo e dispendioso e nel 50% circa dei pazienti non si arriva ad identificare la
mutazione patologica. E’ dunque necessario sviluppare nuove tecniche che permettano ridurre sia tempi e costi delle indagini
sia il numero di pazienti “orfani” di mutazione e dunque privati della possibilità di essere inclusi in trials terapeutici innovativi.
NMD-Chip è un progetto europeo di cui l’Università di Ferrara è partner che ha come scopo quello di studiare i pazienti con
malattie neuromuscolari mediante specifici arrays genomici. Nell’ambito del progetto è stato creato ad oggi un array con 50
geni noti causare malattie neuromuscolari e uno con 40 geni noti causare neuropatie ereditarie. Abbiamo validato l’array per le
malattie neuromuscolari con DNA di pazienti affetti da distrofia di Duchenne identificando la mutazione patologica; abbiamo
inoltre studiato un gruppo di pazienti con miopatia miofibrillare risultati negativi alla analisi molecolare.Il progetto NMD Chip
prevede inoltre che i pazienti risultati negativi per i geni noti vengano studiati con array specifici per geni candidati. Inoltre lo
step finale è lo sviluppo di arrays per la identificazione di piccole mutazioni in tutti i geni indagati. La sensibilità e specificità
diagnostica di questo approccio nei pazienti sarà del 98% e permetterà di ridurre i tempi e i costi delle indagini nelle patologie
neuromuscolari
Two novel mutations in the spastin gene (SPG4) found by DHPLC mutation analysis.
No full textThe most common form of autosomal dominant hereditary spastic paraplegia is caused by mutations in the gene encoding spastin (SPG4), a member of the AAA family of ATPases. In the current study, we designed a denaturing high-performance liquid chromatography based protocol for the analysis of the SPG4 gene. Using this method, we detected two novel missense mutations, 1375AOG (R459G) and 1378COT (R460C), one previously described five bases deletion (1215_1219del) and three polymorphic changes. This study suggests that denaturing high-performance liquid chromatography would be a fast and reliable tool in the investigation of the molecular defects in the SPG4 gene
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