Muestra métricas de impacto externas asociadas a la publicación. Para mayor detalle:
| Indexado |
|
||||
| DOI | 10.3390/BIOMEDICINES12122673 | ||||
| Año | 2024 | ||||
| Tipo | artículo de investigación |
Citas Totales
Autores Afiliación Chile
Instituciones Chile
% Participación
Internacional
Autores
Afiliación Extranjera
Instituciones
Extranjeras
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.
| 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 |
| 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. |