Guidelines for establishing locus specific databases

Vihinen, Mauno; Dunnen, Johan T. den; Dalgleish, Raymond; Cotton, Richard G.H.

doi:10.1002/humu.21646

Cited by 49 publications

(59 citation statements)

References 32 publications

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“…We also engaged in this task because the scientific community has expressed the importance and the need for establishing a dedicated XLMTM database (mutational and clinical). 23 The implementation and curation of this LSDB followed guidelines reported elsewhere, 32,33 and is registered with the HGVS (LSDB list, http://www.hgvs.org/ dblist/glsdb.html).…”

Section: Mtm1-lovdmentioning

confidence: 99%

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Oliveira

Kreß

et al. 2012

Eur J Hum Genet

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Myotubular myopathy (MIM#310400), the X-linked form of Centronuclear myopathy (CNM) is mainly characterized by neonatal hypotonia and inability to maintain unassisted respiration. The MTM1 gene, responsible for this disease, encodes myotubularin -a lipidic phosphatase involved in vesicle trafficking regulation and maturation. Recently, it was shown that myotubularin interacts with desmin, being a major regulator of intermediate filaments. We report the development of a locus-specific database for MTM1 using the Leiden Open Variation database software (http://www.lovd.nl/MTM1), with data collated for 474 mutations identified in 472 patients (by June 2012). Among the entries are a total of 25 new mutations, including a large deletion encompassing introns 2-15. During database implementation it was noticed that no large duplications had been reported. We tested a group of eight uncharacterized CNM patients for this specific type of mutation, by multiple ligationdependent probe amplification (MLPA) analysis. A large duplication spanning exons 1-5 was identified in a boy with a mild phenotype, with results pointing toward possible somatic mosaicism. Further characterization revealed that this duplication causes an in-frame deletion at the mRNA level (r.343_444del). Results obtained with a next generation sequencing approach suggested that the duplication extends into the neighboring MAMLD1 gene and subsequent cDNA analysis detected the presence of a MTM1/MAMLD1 fusion transcript. A complex rearrangement involving the duplication of exon 10 has since been reported, with detection also enabled by MLPA analysis. It is thus conceivable that large duplications in MTM1 may account for a number of CNM cases that have remained genetically unresolved.

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Section: Mtm1-lovdmentioning

confidence: 99%

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Oliveira

Kreß

et al. 2012

Eur J Hum Genet

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“…This seems unreasonable since confirmation in an accredited testing laboratory is not required for publication. However, it is desirable for the development of International Organization for Standardization (ISO) certified standards for databases [6]. Variants are commonly misreported and journal editors and referees should take steps to improve the accuracy of reporting.…”

Section: Further Goals and Challengesmentioning

confidence: 99%

“…The Human Variome Project has developed recommendations for the establishment and maintenance of DNA variant databases (locus-specific databases, LSDB), and practical advice on how to do this [6]. Members of the Human Variome Project have developed a prototype request form for genetic tests with prompts for disease-specific clinical features, and for consent to making test results available to other family members and for database inclusion.…”

Section: The Human Variome Projectmentioning

confidence: 99%

“…Decide whether to use the LOVD database, and Leiden University Medical Center (LUMC) server and management, a different database and server, or a hybrid, for example, the LOVD database hosted on your own institution's server. The server must be secure, and only the database curators and manager should be able to modify database content [6]. LUMC is funded by the European Commission to support LOVD development, infrastructure, software, server, backup, management and security, without cost to the curators or users.…”

Section: The Human Variome Projectmentioning

confidence: 99%

“…7. Describe each variant at the DNA level and its predicted effect on the corresponding mRNA and protein using the appropriate reference sequences [6]. Include both pathogenic and normal variants in the database, and include each variant every time it is found in a different family.…”

Section: The Human Variome Projectmentioning

confidence: 99%

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The Human Variome Project: ensuring the quality of DNA variant databases in inherited renal disease

et al. 2014

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A recent review identified 60 common inherited renal diseases caused by DNA variants in 132 different genes. These diseases can be diagnosed with DNA sequencing, but each gene probably also has a thousand normal variants. Many more normal variants have been characterised by individual laboratories than are reported in the literature or found in publicly accessible collections. At present, testing laboratories must assess each novel change they identify for pathogenicity, even when this has been done elsewhere previously, and the distinction between normal and disease-associated variants is particularly an issue with the recent surge in exomic sequencing and gene discovery projects. The Human Variome Project recommends the establishment of gene-specific DNA variant databases to facilitate the sharing of DNA variants and decisions about likely disease causation. Databases improve diagnostic accuracy and testing efficiency, and reduce costs. They also help with genotype-phenotype correlations and predictive algorithms. The Human Variome Project advocates databases that use standardised descriptions, are up-to-date, include clinical information and are freely available. Currently, the genes affected in the most common inherited renal diseases correspond to 350 different variant databases, many of which are incomplete or have insufficient clinical details for genotype-phenotype correlations. Assistance is needed from nephrologists to maximise the usefulness of these databases for the diagnosis and management of inherited renal disease.

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Human variome project country nodes: Documenting genetic information within a country

Patrinos

Smith²,

Howard³

et al. 2012

Hum. Mutat.

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The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease‐specific databases and a network of Human Variome Project Country Nodes. The latter are nationwide efforts to document the genomic variation reported within a specific population. The development and successful operation of the Human Variome Project Country Nodes are of utmost importance to the success of Human Variome Project's aims and goals because they not only allow the genetic burden of disease to be quantified in different countries, but also provide diagnosticians and researchers access to an up‐to‐date resource that will assist them in their daily clinical practice and biomedical research, respectively. Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council, held on 12th December 2011, during the 2011 Human Variome Project Beijing Meeting. We discuss the steps necessary to maximize the impact of the Country Node effort for developing regional and country‐specific clinical genetics resources and summarize a few well‐coordinated genetic data collection initiatives that would serve as paradigms for similar projects. Hum Mutat 33:1513–1519, 2012. © 2012 Wiley Periodicals, Inc.

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Guidelines for establishing locus specific databases

Cited by 49 publications

References 32 publications

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

The Human Variome Project: ensuring the quality of DNA variant databases in inherited renal disease

Human variome project country nodes: Documenting genetic information within a country

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