Publications by authors named "Joaquim Ribeiro Ventosa"

4 Publications

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Comparison in detection of prodromal Parkinson's disease patients using original and updated MDS research criteria in two independent cohorts.

Parkinsonism Relat Disord 2021 Jun 30;87:48-55. Epub 2021 Apr 30.

Department of Neurology, P. J. Safarik University, Trieda SNP 1, 04011, Kosice, Slovak Republic; Department of Neurology, University Hospital L. Pasteur, Rastislavova 43, 04190, Kosice, Slovak Republic.

Introduction: MDS research criteria for prodromal Parkinson's disease (pPD) were published in 2015 and updated in 2019. We aimed to determine the difference in pPD patient detection rates in two cohorts recruited via gastrointestinal symptoms (PARCAS study) and the presence of a probable REM sleep behaviour disorder (PDBIOM study) using the original and updated criteria.

Methods: We evaluated all risk and prodromal markers, except genetic testing, plasma urate and physical inactivity, in both cohorts and DaT scan, diabetes mellitus type II and cognitive deficit in the PARCAS cohort. Thresholds of 50% probability for possible pPD and 80% for probable pPD were used.

Results: PPD status as identified by the original/updated criteria showed differences for probable pPD (n = 8/9; original/updated criteria) and possible pPD (n = 9/13) in the PARCAS cohort (total n = 158), as well as for probable pPD (n = 19/21) and possible pPD (n = 6/3) in the PDBIOM cohort (total n = 48). A high concordance rate was found between the two criteria sets (p < 0.001 for all groups).

Conclusion: All probable pPD cases remained in the same category after evaluation with both criteria; three possible pPD cases based on the original criteria exceeded the threshold for probable pPD based on the updated criteria, and five possible new pPD cases were detected, with only one shift in the opposite direction. The updated MDS pPD research criteria tend to identify more patients as positive, yet their accuracy needs to be determined in prospective studies.
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June 2021

Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study.

Mov Disord 2021 May 5. Epub 2021 May 5.

Klinik für Neurologie, Asklepios Fachklinikum Stadtroda, Stadtroda, Germany.

Background: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications.

Objectives: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity).

Methods: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses.

Results: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81.

Conclusions: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
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May 2021

Clinically relevant copy-number variants in exome sequencing data of patients with dystonia.

Parkinsonism Relat Disord 2021 03 12;84:129-134. Epub 2021 Feb 12.

Lehrstuhl für Sozialpädiatrie, Technische Universität München, Munich, Germany; Kbo-Kinderzentrum München, Munich, Germany.

Introduction: Next-generation sequencing is now used on a routine basis for molecular testing but studies on copy-number variant (CNV) detection from next-generation sequencing data are underrepresented. Utilizing an existing whole-exome sequencing (WES) dataset, we sought to investigate the contribution of rare CNVs to the genetic causality of dystonia.

Methods: The CNV read-depth analysis tool ExomeDepth was applied to the exome sequences of 953 unrelated patients with dystonia (600 with isolated dystonia and 353 with combined dystonia; 33% with additional neurological involvement). We prioritized rare CNVs that affected known disease genes and/or were known to be associated with defined microdeletion/microduplication syndromes. Pathogenicity assessment of CNVs was based on recently published standards of the American College of Medical Genetics and Genomics and the Clinical Genome Resource.

Results: We identified pathogenic or likely pathogenic CNVs in 14 of 953 patients (1.5%). Of the 14 different CNVs, 12 were deletions and 2 were duplications, ranging in predicted size from 124bp to 17 Mb. Within the deletion intervals, BRPF1, CHD8, DJ1, EFTUD2, FGF14, GCH1, PANK2, SGCE, UBE3A, VPS16, WARS2, and WDR45 were determined as the most clinically relevant genes. The duplications involved chromosomal regions 6q21-q22 and 15q11-q13. CNV analysis increased the diagnostic yield in the total cohort from 18.4% to 19.8%, as compared to the assessment of single-nucleotide variants and small insertions and deletions alone.

Conclusions: WES-based CNV analysis in dystonia is feasible, increases the diagnostic yield, and should be combined with the assessment of single-nucleotide variants and small insertions and deletions.
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March 2021