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Studying Rare Movement Disorders: From Whole-Exome Sequencing to New Diagnostic and Therapeutic Approaches in a Modern Genetic Clinic
Indexado
WoS WOS:001387665000001
Scopus SCOPUS_ID:85213222456
DOI 10.3390/BIOMEDICINES12122673
Año 2024
Tipo artículo de investigación

Citas Totales

Autores Afiliación Chile

Instituciones Chile

% Participación
Internacional

Autores
Afiliación Extranjera

Instituciones
Extranjeras


Abstract



Background: Rare movement disorders often have a genetic etiology. New technological advances have increased the odds of achieving genetic diagnoses: next-generation sequencing (NGS) (whole-exome sequencing-WES; whole-genome sequencing-WGS) and long-read sequencing (LRS). In 2017, we launched a WES program for patients with rare movement disorders of suspected genetic etiology. We aim to describe the accumulated experience of a modern movement disorder genetic clinic, highlighting how different available genetic tests might be prioritized according to the clinical phenotype and pattern of inheritance. Methods: Participants were studied through WES analysis. Descriptive statistics, including the mean, standard deviation, counts, and percentages, were used to summarize demographic and clinical characteristics in all subjects and with each type of result [pathogenic or likely pathogenic, variants of uncertain significance (VUS), negative]. Results: We studied 88 patients (93.2% Caucasian, 5.72% African American, and 1.08% Hispanic or Latino). After excluding six family members from four index participants, the diagnostic yield of WES reached 27% (22/82 probands). The age at onset was significantly lower in patients with pathogenic/likely pathogenic variants. The most common clinical phenotypes were ataxia and parkinsonism. Dystonia, ataxia, leukoencephalopathy, and parkinsonism were associated with most genetic diagnoses. Conclusions: We propose a comprehensive protocol with decision tree testing for WGS and LRS, a return of results, and a re-analysis of inconclusive genetic data to increase the diagnostic yield of patients with rare neurogenetic disorders.

Revista



Revista ISSN
Biomedicines 2227-9059

Métricas Externas



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Disciplinas de Investigación



WOS
Biochemistry & Molecular Biology
Pharmacology & Pharmacy
Medicine, Research & Experimental
Scopus
Biochemistry, Genetics And Molecular Biology (All)
Medicine (Miscellaneous)
SciELO
Sin Disciplinas

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Publicaciones WoS (Ediciones: ISSHP, ISTP, AHCI, SSCI, SCI), Scopus, SciELO Chile.

Colaboración Institucional



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Autores - Afiliación



Ord. Autor Género Institución - País
1 Marsili, Luca - UNIV CINCINNATI - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
2 Duque, Kevin R. - UNIV CINCINNATI - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
3 Abanto, Jesus - UNIV CINCINNATI - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
4 Paredes, Nathaly O. Chinchihualpa - UNIV CINCINNATI - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
4 Chinchihualpa Paredes, Nathaly O. - University of Cincinnati College of Medicine - Estados Unidos
5 Duker, Andrew P. - UNIV CINCINNATI - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
6 Collins, Kathleen - Childrens Hosp Med Ctr - Estados Unidos
Cincinnati Children's Hospital Medical Center - Estados Unidos
7 MIRANDA-SALAS, MARCELO DAVID Hombre Clin Meds - Chile
Fdn Diag - Chile
Clinica Meds, Chile - Chile
Fundación Diagnosis - Chile
8 Bustamante, M. Leonor - Clin Meds - Chile
Fdn Diag - Chile
Universidad de Chile - Chile
Clinica Meds, Chile - Chile
Fundación Diagnosis - Chile
9 Pauciulo, Michael - Childrens Hosp Med Ctr - Estados Unidos
Cincinnati Children's Hospital Medical Center - Estados Unidos
10 Dixon, Michael - Childrens Hosp Med Ctr - Estados Unidos
UNIV CINCINNATI - Estados Unidos
Cincinnati Children's Hospital Medical Center - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
11 Chaib, Hassan - Childrens Hosp Med Ctr - Estados Unidos
UNIV CINCINNATI - Estados Unidos
Cincinnati Children's Hospital Medical Center - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
12 Perez-Maturo, Josefina - Hosp JM Ramos Mejia - Argentina
Universidad Austral de Chile - Argentina
Hospital J.M. Ramos Mejia, Buenos Aires - Argentina
13 Hill, Emily J. - UNIV CINCINNATI - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
14 Espay, Alberto J. Hombre UNIV CINCINNATI - Estados Unidos
University of Cincinnati College of Medicine - Estados Unidos
15 Kauffman, Marcelo A. Hombre Hosp JM Ramos Mejia - Argentina
Universidad Austral de Chile - Argentina
Hospital J.M. Ramos Mejia, Buenos Aires - Argentina

Muestra la afiliación y género (detectado) para los co-autores de la publicación.

Financiamiento



Fuente
Discover Together Biobank
Genomics Sequencing Facility

Muestra la fuente de financiamiento declarada en la publicación.

Agradecimientos



Agradecimiento
We thank the patients and families for their support and collaboration. This study used biospecimen processing and storage services from the Discover Together Biobank at Cincinnati Children's Research Foundation. We thank the Discover Together Biobank for their support of this work (RRID: SCR_022632), and the Genomics Sequencing Facility (RRID:SCR_022630) for library preparation and sequencing.

Muestra la fuente de financiamiento declarada en la publicación.