Launching the movement disorders society genetic mutation database (MDSGene)

Lill, Christina M.; Mashychev, Andriy; Hartmann, Corinna; Lohmann, Katja; Marras, Connie; Lang, Anthony E.; Klein, Christine; Bertram, Lars

doi:10.1002/mds.26651

Cited by 61 publications

(59 citation statements)

References 2 publications

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“…As the term SCA is quite strongly associated with dominant ataxias, we decided to use the ATX prefix instead. In the International Parkinson and Movement Disorder Society Genetic Mutation Online Database (MDSGene; available at http://www.mdsgene.org), which systematically links reported mutations to movement disorder phenotypes, the dominant ataxias will also carry the ATX prefix.…”

Section: Review Processmentioning

confidence: 99%

The genetic nomenclature of recessive cerebellar ataxias

et al. 2018

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The recessive cerebellar ataxias are a large group of degenerative and metabolic disorders, the diagnostic management of which is difficult because of the enormous clinical and genetic heterogeneity. Because of several limitations, the current classification systems provide insufficient guidance for clinicians and researchers. Here, we propose a new nomenclature for the genetically confirmed recessive cerebellar ataxias according to the principles and criteria laid down by the International Parkinson and Movement Disorder Society Task Force on Classification and Nomenclature of Genetic Movement Disorders. We apply stringent criteria for considering an association between gene and phenotype to be established. The newly proposed list of recessively inherited cerebellar ataxias includes 62 disorders that were assigned an ATX prefix, followed by the gene name, because these typically present with ataxia as a predominant and/or consistent feature. An additional 30 disorders that often combine ataxia with a predominant or consistent other movement disorder received a double prefix (e.g., ATX/HSP). We also identified a group of 89 entities that usually present with complex nonataxia phenotypes, but may occasionally present with cerebellar ataxia. These are listed separately without the ATX prefix. This new, transparent and adaptable nomenclature of the recessive cerebellar ataxias will facilitate the clinical recognition of recessive ataxias, guide diagnostic testing in ataxia patients, and help in interpreting genetic findings. © 2018 International Parkinson and Movement Disorder Society.

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Section: Review Processmentioning

confidence: 99%

The genetic nomenclature of recessive cerebellar ataxias

et al. 2018

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“…Our group has recently developed and launched the Movement Disorder Society Genetic mutation database (MDSGene; http://www.mdsgene.org). MDSGene aims to provide a comprehensive online resource linking reported genetic mutations with movement disorder phenotypes and other demographic and clinical information. This review follows MDSGene's standardized data extraction protocol optimized for hereditary movement disorders and (1) presents an overview on the currently available phenotypic and genotypic data on autosomal recessive PD, (2) assesses the pathogenicity of reported potentially causative mutations, (3) compares published data across the 3 genes and provides stratified analyses in selected patient subgroups, (4) evaluates the extent and potential impact of missing data on the interpretation of the results, and (5) identifies potential consequences for genetic counseling in clinical practice, as well as resulting new research leads.…”

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confidence: 99%

Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review

et al. 2018

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This first comprehensive MDSGene review is devoted to the 3 autosomal recessive Parkinson's disease forms: PARK-Parkin, PARK-PINK1, and PARK-DJ1. It followed MDSGene's standardized data extraction protocol and screened a total of 3652 citations and is based on fully curated phenotypic and genotypic data on >1100 patients with recessively inherited PD because of 221 different disease-causing mutations in Parkin, PINK1, or DJ1. All these data are also available in an easily searchable online database (www.mdsgene.org), which also provides descriptive summary statistics on phenotypic and genetic data. Despite the high degree of missingness of phenotypic features and unsystematic reporting of genotype data in the original literature, the present review recapitulates many of the previously described findings including early onset (median age at onset of ∼30 years for carriers of at least 2 mutations in any of the 3 genes) of an overall clinically typical form of PD with excellent treatment response, dystonia and dyskinesia being relatively common and cognitive decline relatively uncommon. However, when comparing actual data with common expert knowledge in previously published reviews, we detected several discrepancies. We conclude that systematic reporting of phenotypes is a pressing need in light of increasingly available molecular genetic testing and the emergence of first gene-specific therapies entering clinical trials. © 2018 International Parkinson and Movement Disorder Society.

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“…The International Parkinson and Movement Disorder Society Genetic mutation database (MDSGene; http://www.mdsgene.org) aims to systematically collect clinical and genetic information for movement disorder patients who have pathogenic mutations. In this study, we present a systematic MDSGene review and devote it to autosomal‐dominant PD across the three disorders, PARK‐ SNCA , PARK‐ LRRK2 , and PARK‐ VPS35 …”

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confidence: 99%

Genotype‐phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review

et al. 2018

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This comprehensive MDSGene review is devoted to the three autosomal‐dominant PD forms: PARK‐SNCA, PARK‐LRRK2, and PARK‐VPS35. It follows MDSGene's standardized data extraction protocol, screened a total of 2,972 citations, and is based on fully curated phenotypic and genotypic data on 937 patients with dominantly inherited PD attributed to 44 different mutations in SNCA, LRRK2, or VPS35. All of these data are also available in an easily searchable online database (http://www.mdsgene.org), which additionally provides descriptive summary statistics on phenotypic and genetic data. Despite the high degree of missingness of phenotypic features and unsystematic reporting of genotype data in the original literature, the present review recapitulates many of the previously described findings including later onset of disease (median age at onset: ∼49 years) compared to recessive forms of PD of an overall excellent treatment response. Our systematic review validates previous reports showing that SNCA mutation carriers have a younger age at onset compared to LRRK2 and VPS35 (P < 0.001). SNCA mutation carriers often have additional psychiatric symptoms, and although not exclusive to only LRRK2 or VPS35 mutation carriers, LRRK2 mutation carriers have a typical form of PD, and, lastly, VPS35 mutation carriers have good response to l‐dopa. © 2018 International Parkinson and Movement Disorder Society

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Launching the movement disorders society genetic mutation database (MDSGene)

Cited by 61 publications

References 2 publications

The genetic nomenclature of recessive cerebellar ataxias

The genetic nomenclature of recessive cerebellar ataxias

Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review

Genotype‐phenotype relations for the Parkinson's disease genes SNCA, LRRK2, VPS35: MDSGene systematic review

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