Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice

Autores
Millar Vernetti, Patricio Alejandro; Ruiz Yanzi, María Agustina; Rossi, Malco Damian; Merello, Marcelo Jorge
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Use of next-generation sequencing, including whole-exome sequencing (WES) has not only allowed diagnosis to be reached in patients with atypical phenotypes, but also led to detection of new pathogenic variants, as well as to linking of specific clinical manifestations to known diseases. Nevertheless, controversy persists regarding routine implementation of WES in clinical practice [1, 2]. Interpretation of results and understanding of the clinical relevance can be problematic, particularly in cases of variants of unknown significance (VUS) [3]. Application of WES can however be cost-effective when based on appropriate clinical criteria, and may even reduce costs by limiting unnecessary complementary studies [4]. Although slowly becoming more financially accessible, WES remains an expensive study. Inappropriate or indiscriminate use may increase overall healthcare costs, without providing significant benefit. In addition, WES does not detect large gene deletions or duplications, or expansion disorders such as triplet repeat expansions, or genes located on non-coding segments of the genome (introns), and therefore is not useful to diagnose diseases caused by these particular mutations [1, 2]. The diagnostic yield of WES in different case series of adult patients with neurological diseases has consistently been around 30% [5, 6]. In children, similar [7–9], or somewhat higher values have been reported [10]. More specifically in movement disorders, a study including 378 patients with atypical or combined phenotypes, found the diagnostic yield was 22% [11].
Fil: Millar Vernetti, Patricio Alejandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Ruiz Yanzi, María Agustina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Rossi, Malco Damian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Merello, Marcelo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Materia
CONTROVERSIES
DIAGNOSIS
GENETICS
WES
WHOLE-EXOME SEQUENCING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/216393

id CONICETDig_d61f5413d49e82de101b311d64fda3ca
oai_identifier_str oai:ri.conicet.gov.ar:11336/216393
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical PracticeMillar Vernetti, Patricio AlejandroRuiz Yanzi, María AgustinaRossi, Malco DamianMerello, Marcelo JorgeCONTROVERSIESDIAGNOSISGENETICSWESWHOLE-EXOME SEQUENCINGhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Use of next-generation sequencing, including whole-exome sequencing (WES) has not only allowed diagnosis to be reached in patients with atypical phenotypes, but also led to detection of new pathogenic variants, as well as to linking of specific clinical manifestations to known diseases. Nevertheless, controversy persists regarding routine implementation of WES in clinical practice [1, 2]. Interpretation of results and understanding of the clinical relevance can be problematic, particularly in cases of variants of unknown significance (VUS) [3]. Application of WES can however be cost-effective when based on appropriate clinical criteria, and may even reduce costs by limiting unnecessary complementary studies [4]. Although slowly becoming more financially accessible, WES remains an expensive study. Inappropriate or indiscriminate use may increase overall healthcare costs, without providing significant benefit. In addition, WES does not detect large gene deletions or duplications, or expansion disorders such as triplet repeat expansions, or genes located on non-coding segments of the genome (introns), and therefore is not useful to diagnose diseases caused by these particular mutations [1, 2]. The diagnostic yield of WES in different case series of adult patients with neurological diseases has consistently been around 30% [5, 6]. In children, similar [7–9], or somewhat higher values have been reported [10]. More specifically in movement disorders, a study including 378 patients with atypical or combined phenotypes, found the diagnostic yield was 22% [11].Fil: Millar Vernetti, Patricio Alejandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ruiz Yanzi, María Agustina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Rossi, Malco Damian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Merello, Marcelo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaUbiquity Press2022-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216393Millar Vernetti, Patricio Alejandro; Ruiz Yanzi, María Agustina; Rossi, Malco Damian; Merello, Marcelo Jorge; Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice; Ubiquity Press; Tremor and Other Hyperkinetic Movements; 12; 1; 4-2022; 1-92160-8288CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://tremorjournal.org/articles/10.5334/tohm.678info:eu-repo/semantics/altIdentifier/doi/10.5334/tohm.678info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:28Zoai:ri.conicet.gov.ar:11336/216393instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:10:29.25CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
title Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
spellingShingle Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
Millar Vernetti, Patricio Alejandro
CONTROVERSIES
DIAGNOSIS
GENETICS
WES
WHOLE-EXOME SEQUENCING
title_short Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
title_full Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
title_fullStr Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
title_full_unstemmed Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
title_sort Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice
dc.creator.none.fl_str_mv Millar Vernetti, Patricio Alejandro
Ruiz Yanzi, María Agustina
Rossi, Malco Damian
Merello, Marcelo Jorge
author Millar Vernetti, Patricio Alejandro
author_facet Millar Vernetti, Patricio Alejandro
Ruiz Yanzi, María Agustina
Rossi, Malco Damian
Merello, Marcelo Jorge
author_role author
author2 Ruiz Yanzi, María Agustina
Rossi, Malco Damian
Merello, Marcelo Jorge
author2_role author
author
author
dc.subject.none.fl_str_mv CONTROVERSIES
DIAGNOSIS
GENETICS
WES
WHOLE-EXOME SEQUENCING
topic CONTROVERSIES
DIAGNOSIS
GENETICS
WES
WHOLE-EXOME SEQUENCING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Use of next-generation sequencing, including whole-exome sequencing (WES) has not only allowed diagnosis to be reached in patients with atypical phenotypes, but also led to detection of new pathogenic variants, as well as to linking of specific clinical manifestations to known diseases. Nevertheless, controversy persists regarding routine implementation of WES in clinical practice [1, 2]. Interpretation of results and understanding of the clinical relevance can be problematic, particularly in cases of variants of unknown significance (VUS) [3]. Application of WES can however be cost-effective when based on appropriate clinical criteria, and may even reduce costs by limiting unnecessary complementary studies [4]. Although slowly becoming more financially accessible, WES remains an expensive study. Inappropriate or indiscriminate use may increase overall healthcare costs, without providing significant benefit. In addition, WES does not detect large gene deletions or duplications, or expansion disorders such as triplet repeat expansions, or genes located on non-coding segments of the genome (introns), and therefore is not useful to diagnose diseases caused by these particular mutations [1, 2]. The diagnostic yield of WES in different case series of adult patients with neurological diseases has consistently been around 30% [5, 6]. In children, similar [7–9], or somewhat higher values have been reported [10]. More specifically in movement disorders, a study including 378 patients with atypical or combined phenotypes, found the diagnostic yield was 22% [11].
Fil: Millar Vernetti, Patricio Alejandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Ruiz Yanzi, María Agustina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Rossi, Malco Damian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Merello, Marcelo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
description Use of next-generation sequencing, including whole-exome sequencing (WES) has not only allowed diagnosis to be reached in patients with atypical phenotypes, but also led to detection of new pathogenic variants, as well as to linking of specific clinical manifestations to known diseases. Nevertheless, controversy persists regarding routine implementation of WES in clinical practice [1, 2]. Interpretation of results and understanding of the clinical relevance can be problematic, particularly in cases of variants of unknown significance (VUS) [3]. Application of WES can however be cost-effective when based on appropriate clinical criteria, and may even reduce costs by limiting unnecessary complementary studies [4]. Although slowly becoming more financially accessible, WES remains an expensive study. Inappropriate or indiscriminate use may increase overall healthcare costs, without providing significant benefit. In addition, WES does not detect large gene deletions or duplications, or expansion disorders such as triplet repeat expansions, or genes located on non-coding segments of the genome (introns), and therefore is not useful to diagnose diseases caused by these particular mutations [1, 2]. The diagnostic yield of WES in different case series of adult patients with neurological diseases has consistently been around 30% [5, 6]. In children, similar [7–9], or somewhat higher values have been reported [10]. More specifically in movement disorders, a study including 378 patients with atypical or combined phenotypes, found the diagnostic yield was 22% [11].
publishDate 2022
dc.date.none.fl_str_mv 2022-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/216393
Millar Vernetti, Patricio Alejandro; Ruiz Yanzi, María Agustina; Rossi, Malco Damian; Merello, Marcelo Jorge; Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice; Ubiquity Press; Tremor and Other Hyperkinetic Movements; 12; 1; 4-2022; 1-9
2160-8288
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216393
identifier_str_mv Millar Vernetti, Patricio Alejandro; Ruiz Yanzi, María Agustina; Rossi, Malco Damian; Merello, Marcelo Jorge; Genetic Diagnosis in Movement Disorders. Use of Whole-Exome Sequencing in Clinical Practice; Ubiquity Press; Tremor and Other Hyperkinetic Movements; 12; 1; 4-2022; 1-9
2160-8288
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://tremorjournal.org/articles/10.5334/tohm.678
info:eu-repo/semantics/altIdentifier/doi/10.5334/tohm.678
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Ubiquity Press
publisher.none.fl_str_mv Ubiquity Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842270121337290752
score 13.13397