Genome sequencing reanalysis increases the diagnostic yield in dystonia.

Autor:	Fellner A; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; The Neurogenetics Clinic, Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. Electronic address: avi.fellner@gmail.com., Wali GM; Neurospecialities Centre, Belgaum, India., Mahant N; Movement Disorders Unit, Neurology Department, Westmead Hospital, Westmead, NSW, Australia., Grosz BR; Northcott Neuroscience Laboratory, ANZAC Research Institute SLHD, Concord, NSW, Australia., Ellis M; Northcott Neuroscience Laboratory, ANZAC Research Institute SLHD, Concord, NSW, Australia., Narayanan RK; Northcott Neuroscience Laboratory, ANZAC Research Institute SLHD, Concord, NSW, Australia., Ng K; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia., Davis RL; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Neurogenetics, Kolling Institute, Faculty of Medicine and Health, University of Sydney and Northern Sydney Local Health District, St. Leonards, NSW, Australia., Tchan MC; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Genetic Medicine, Westmead Hospital, Westmead, NSW, Australia., Kotschet K; Clinical Neurosciences, St. Vincent's Hospital, Melbourne, Australia., Yeow D; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Concord Repatriation General Hospital, Sydney, NSW, Australia; Molecular Medicine Laboratory, Concord Repatriation General Hospital, Concord, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia., Rudaks LI; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Concord Repatriation General Hospital, Sydney, NSW, Australia; Molecular Medicine Laboratory, Concord Repatriation General Hospital, Concord, NSW, Australia; Department of Clinical Genetics, Royal North Shore Hospital, St. Leonards, NSW, Australia., Siow SF; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Clinical Genetics, Royal North Shore Hospital, St. Leonards, NSW, Australia., Wali G; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Neurogenetics, Kolling Institute, Faculty of Medicine and Health, University of Sydney and Northern Sydney Local Health District, St. Leonards, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia., Yiannikas C; Department of Neurology, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia; Department of Neurology, Concord Repatriation General Hospital, Sydney, NSW, Australia., Hobbs M; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Copty J; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Geaghan M; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Darveniza P; Department of Neurology, St. Vincent's Hospital, Darlinghurst, NSW, Australia., Liang C; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia., Williams LJ; Movement Disorders Unit, Neurology Department, Westmead Hospital, Westmead, NSW, Australia., Chang FCF; Movement Disorders Unit, Neurology Department, Westmead Hospital, Westmead, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Morales-Briceño H; Movement Disorders Unit, Neurology Department, Westmead Hospital, Westmead, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Tisch S; Department of Neurology, St. Vincent's Hospital, Darlinghurst, NSW, Australia; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, NSW, Australia., Hayes M; Department of Neurology, Concord Repatriation General Hospital, Sydney, NSW, Australia., Whyte S; Department of Neurology, Gosford Hospital, Gosford, Australia., Kummerfeld S; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia., Kennerson ML; Northcott Neuroscience Laboratory, ANZAC Research Institute SLHD, Concord, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Molecular Medicine Laboratory, Concord Repatriation General Hospital, Concord, NSW, Australia., Cowley MJ; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, NSW, Australia; Children's Cancer Institute, University of New South Wales, Sydney, Australia., Fung VSC; Movement Disorders Unit, Neurology Department, Westmead Hospital, Westmead, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Sue CM; Department of Neurology, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, NSW, Australia; Department of Neurogenetics, Kolling Institute, Faculty of Medicine and Health, University of Sydney and Northern Sydney Local Health District, St. Leonards, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, NSW, Australia., Kumar KR; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Concord Repatriation General Hospital, Sydney, NSW, Australia; Molecular Medicine Laboratory, Concord Repatriation General Hospital, Concord, NSW, Australia; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, NSW, Australia. Electronic address: k.kumar@garvan.org.au.
Jazyk:	angličtina
Zdroj:	Parkinsonism & related disorders [Parkinsonism Relat Disord] 2024 Jul; Vol. 124, pp. 107010. Date of Electronic Publication: 2024 May 14.
DOI:	10.1016/j.parkreldis.2024.107010
Abstrakt:	Purpose: We investigated the contribution of genomic data reanalysis to the diagnostic yield of dystonia patients who remained undiagnosed after prior genome sequencing. Methods: Probands with heterogeneous dystonia phenotypes who underwent initial genome sequencing (GS) analysis in 2019 were included in the reanalysis, which was performed through gene-specific discovery collaborations and systematic genomic data reanalysis. Results: Initial GS analysis in 2019 (n = 111) identified a molecular diagnosis in 11.7 % (13/111) of cases. Reanalysis between 2020 and 2023 increased the diagnostic yield by 7.2 % (8/111); 3.6 % (4/111) through focused gene-specific clinical correlation collaborative efforts [VPS16 (two probands), AOPEP and POLG], and 3.6 % (4/111) by systematic reanalysis completed in 2023 [NUS1 (two probands) and DDX3X variants, and a microdeletion encompassing VPS16]. Seven of these patients had a high phenotype-based dystonia score ≥3. Notable unverified findings in four additional cases included suspicious variants of uncertain significance in FBXL4 and EIF2AK2, and potential phenotypic expansion associated with SLC2A1 and TREX1 variants. Conclusion: GS data reanalysis increased the diagnostic yield from 11.7 % to 18.9 %, with potential extension up to 22.5 %. While optimal timing for diagnostic reanalysis remains to be determined, this study demonstrates that periodic re-interrogation of dystonia GS datasets can provide additional genetic diagnoses, which may have significant implications for patients and their families. Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kishore Raj Kumar reports financial support was provided by the Ainsworth 4 Foundation. Stephen Tisch reports a relationship with Medtronic that includes: consulting or advisory and speaking and lecture fees. Stephen Tisch reports a relationship with Boston Scientific that includes: consulting or advisory and speaking and lecture fees. Stephen Tisch reports a relationship with Seqirus Pharmaceuticals that includes: consulting or advisory and speaking and lecture fees. Carolyn M. Sue reports a relationship with Living Cell Technologies Ltd. that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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