Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Medientyp: E-Artikel
Titel: Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort
Beteiligte: Vollstedt, Eva‐Juliane; Schaake, Susen; Lohmann, Katja; Padmanabhan, Shalini; Brice, Alexis; Lesage, Suzanne; Tesson, Christelle; Vidailhet, Marie; Wurster, Isabel; Hentati, Faycel; Mirelman, Anat; Giladi, Nir; Marder, Karen; Waters, Cheryl; Fahn, Stanley; Kasten, Meike; Brüggemann, Norbert; Borsche, Max; Foroud, Tatiana; Tolosa, Eduardo; Garrido, Alicia; Annesi, Grazia; Gagliardi, Monica; Bozi, Maria; [...]
Erschienen: Wiley, 2023
Erschienen in: Movement Disorders
Sprache: Englisch
DOI: 10.1002/mds.29288
ISSN: 0885-3185; 1531-8257
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>As gene‐targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial‐ready cohorts is limited.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD‐linked variants; (2) provide harmonized and quality‐controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a worldwide, systematic online survey to collect individual‐level data on individuals with PD‐linked variants in <jats:italic>SNCA</jats:italic>, <jats:italic>LRRK2</jats:italic>, <jats:italic>VPS35</jats:italic>, <jats:italic>PRKN</jats:italic>, <jats:italic>PINK1</jats:italic>, <jats:italic>DJ‐1</jats:italic>, as well as selected pathogenic and risk variants in <jats:italic>GBA</jats:italic> and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 <jats:italic>LRRK2</jats:italic>, 115 <jats:italic>SNCA</jats:italic>, 23 <jats:italic>VPS35</jats:italic>, 429 <jats:italic>PRKN</jats:italic>, 75 <jats:italic>PINK1</jats:italic>, 13 <jats:italic>DJ‐1</jats:italic>, and 1224 <jats:italic>GBA</jats:italic>) and 703 were unaffected (ie, 328 <jats:italic>LRRK2</jats:italic>, 32 <jats:italic>SNCA</jats:italic>, 3 <jats:italic>VPS35</jats:italic>, 1 <jats:italic>PRKN</jats:italic>, 1 <jats:italic>PINK1</jats:italic>, and 338 <jats:italic>GBA</jats:italic>). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD‐linked variants; (2) provide harmonized and quality‐controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene‐targeted clinical trials. © 2023 The Authors. <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</jats:p></jats:sec>

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