Carolin Anna Maria Koriath, Fernando Guntoro, Penelope Norsworthy, Egor Dolzhenko, Michael Eberle, Davina J Hensman Moss, Michael Flower, Holger Hummerich, Anne Elizabeth Rosser, Sarah J Tabrizi, Simon Mead, Edward J Wild
{"title":"亨廷顿氏病表型综合征再探：临床比较与新一代测序探索。","authors":"Carolin Anna Maria Koriath, Fernando Guntoro, Penelope Norsworthy, Egor Dolzhenko, Michael Eberle, Davina J Hensman Moss, Michael Flower, Holger Hummerich, Anne Elizabeth Rosser, Sarah J Tabrizi, Simon Mead, Edward J Wild","doi":"10.1136/jnnp-2024-333602","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Genetic testing for Huntington's disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC.</p><p><strong>Methods: </strong>Clinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis.</p><p><strong>Results: </strong>HDPC prevalence was estimated at 2.3-2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified one <i>ATXN1</i> expansion in a patient with HDPC.</p><p><strong>Conclusions: </strong>The HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC.</p>","PeriodicalId":16418,"journal":{"name":"Journal of Neurology, Neurosurgery, and Psychiatry","volume":null,"pages":null},"PeriodicalIF":8.7000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration.\",\"authors\":\"Carolin Anna Maria Koriath, Fernando Guntoro, Penelope Norsworthy, Egor Dolzhenko, Michael Eberle, Davina J Hensman Moss, Michael Flower, Holger Hummerich, Anne Elizabeth Rosser, Sarah J Tabrizi, Simon Mead, Edward J Wild\",\"doi\":\"10.1136/jnnp-2024-333602\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Genetic testing for Huntington's disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC.</p><p><strong>Methods: </strong>Clinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis.</p><p><strong>Results: </strong>HDPC prevalence was estimated at 2.3-2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified one <i>ATXN1</i> expansion in a patient with HDPC.</p><p><strong>Conclusions: </strong>The HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC.</p>\",\"PeriodicalId\":16418,\"journal\":{\"name\":\"Journal of Neurology, Neurosurgery, and Psychiatry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.7000,\"publicationDate\":\"2024-10-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology, Neurosurgery, and Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jnnp-2024-333602\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology, Neurosurgery, and Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jnnp-2024-333602","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration.
Background: Genetic testing for Huntington's disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC.
Methods: Clinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis.
Results: HDPC prevalence was estimated at 2.3-2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified one ATXN1 expansion in a patient with HDPC.
Conclusions: The HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC.
期刊介绍：
The Journal of Neurology, Neurosurgery & Psychiatry (JNNP) aspires to publish groundbreaking and cutting-edge research worldwide. Covering the entire spectrum of neurological sciences, the journal focuses on common disorders like stroke, multiple sclerosis, Parkinson’s disease, epilepsy, peripheral neuropathy, subarachnoid haemorrhage, and neuropsychiatry, while also addressing complex challenges such as ALS. With early online publication, regular podcasts, and an extensive archive collection boasting the longest half-life in clinical neuroscience journals, JNNP aims to be a trailblazer in the field.
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