| 1. |
- Bladen, Catherine L., et al.
(författare)
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The TREAT-NMD Duchenne Muscular Dystrophy Registries : Conception, Design, and Utilization by Industry and Academia
- 2013
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 34:11, s. 1449-1457
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Tidskriftsartikel (refereegranskat)abstract
- Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence<5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.
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| 2. |
- Byrne, Myles, et al.
(författare)
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VarioML framework for comprehensive variation data representation and exchange
- 2012
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 13:254
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. Results: The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e. g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. Conclusions: VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity.
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| 3. |
- Böhm, Johann, et al.
(författare)
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Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.
- 2012
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 33:6, s. 949-59
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Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.
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| 4. |
- Laurie, Steven, et al.
(författare)
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The RD-Connect Genome-Phenome Analysis Platform : Accelerating diagnosis, research, and gene discovery for rare diseases
- 2022
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:6, s. 717-733
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Tidskriftsartikel (refereegranskat)abstract
- Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.
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| 5. |
- Saunders, Gary, et al.
(författare)
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Leveraging European infrastructures to access 1 million human genomes by 2022
- 2019
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Ingår i: Nature reviews genetics. - : Springer Nature. - 1471-0056 .- 1471-0064. ; 20:11, s. 693-701
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Tidskriftsartikel (refereegranskat)abstract
- Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition of this challenge, 21 European countries recently signed a declaration to transnationally share data on at least 1 million human genomes by 2022. In this Roadmap, we identify the challenges of data sharing across borders and demonstrate that European research infrastructures are well-positioned to support the rapid implementation of widespread genomic data access.
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