TY - JOUR
T1 - Genotype–Phenotype Relations for Isolated Dystonia Genes: MDSGene Systematic Review
AU - Lange, Lara M.
AU - Junker, Johanna
AU - Loens, Sebastian
AU - Baumann, Hauke
AU - Olschewski, Luisa
AU - Schaake, Susen
AU - Madoev, Harutyun
AU - Petkovic, Sonja
AU - Kuhnke, Neele
AU - Kasten, Meike
AU - Westenberger, Ana
AU - Domingo, Aloysius
AU - Marras, Connie
AU - König, Inke R.
AU - Camargos, Sarah
AU - Ozelius, Laurie J.
AU - Klein, Christine
AU - Lohmann, Katja
N1 - Funding Information:
Lara Lange is employed by UKSH Lübeck. Johanna Junker is employed by UKSH Lübeck. Sebastian Loens has employment within the “DysTract‐GermanDystonia Translational Research and Therapy Consortium” project, funded by the German Federal Ministry of Education and Research (BMBF). Hauke Baumann is employed by University of Lübeck. Luisa Olschewski is a student at the University of Lübeck. Susen Schaake is employed by UKSH Lübeck. Harutyun Madoev is employed by UKSH Lübeck. Sonja Petkovic has received a travel grant from MDS and is employed by UKSH Lübeck. Neele Kuhnke is a student assistant at the University of Lübeck has received grants from the German Research Foundation and is employed by the University of Lübeck, UKSH Lübeck. Ana Westenberger is a consultant for medical writing at CENTOGENE GmbH, has received a grant from the German Research Foundation (FOR2488), and is employed by UKSH Lübeck. Aloysius Domingo is employed by Massachusetts General Hospital. Connie Marras is a consultant for Acorda Therapeutics, has received honoraria for teaching from EMD Serono, steering committee for National Parkinson Foundation, has received grants from the Michael J. Fox Foundation, Canadian Institutes of Health Research, Movement Disorder Society, and National Institutes of Health, and is employed by the University Health Network. Inke R. König has received grants from the German Research Foundation and is employed by the University of Lübeck. Sarah Camargos is on the advisory board of Teva Pharmaceuticals, has received grants from ROCHE and Teva Pharmaceuticals, and is employed by the Federal University of Minas Gerais. Laurie J. Ozelius is on the advisory boards of NSDA, BEBRF, and AHCF, has received grants from the NIH and CCXDP, is employed by Massachusetts General Hospital, and has received royalties from Athena Diagnostics. Christine Klein, MD, is a medical adviser to Centogene for genetic testing of movement disorders excluding Parkinson's disease, has received honoraria from the Scientific Advisory Board of the Else Kroener Fresenius Foundation, has received grants from the Hermann and Lilly Schilling Foundation; the German Research Foundation, the BMBF, the German Research Foundation, and the European Community and intramural funds from the University of Luebeck, is employed by the University of Luebeck, and has received royalties from Oxford University Press. Katja Lohmann has received grants from the German Research Foundation, Movement Disorder Society, Damp Foundation, and the Michael J. Fox Foundation (GP2 project) and is employed by the University of Lübeck.
Publisher Copyright:
© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - This comprehensive MDSGene review is devoted to 7 genes — TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA — mutations in which may cause isolated dystonia. It followed MDSGene's standardized data extraction protocol and screened a total of ~1200 citations. Phenotypic and genotypic data on ~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics.
AB - This comprehensive MDSGene review is devoted to 7 genes — TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA — mutations in which may cause isolated dystonia. It followed MDSGene's standardized data extraction protocol and screened a total of ~1200 citations. Phenotypic and genotypic data on ~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics.
UR - http://www.scopus.com/inward/record.url?scp=85099944361&partnerID=8YFLogxK
U2 - 10.1002/mds.28485
DO - 10.1002/mds.28485
M3 - Scientific review articles
AN - SCOPUS:85099944361
SN - 0885-3185
JO - Movement Disorders
JF - Movement Disorders
ER -