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

Michael Zech; Robert Jech; Sylvia Boesch; Matej Škorvánek; Ján Necpál; Jana Švantnerová; Matias Wagner; Ariane Sadr-Nabavi; Felix Distelmaier; Martin Krenn; Tereza Serranová; Irena Rektorová; Petra Havránková; Alexandra Mosejová; Iva Příhodová; Jana Šarláková; Kristína Kulcsarová; Olga Ulmanová; Karel Bechyně; Miriam Ostrozovičová; Vladimír Haň; Joaquim Ribeiro Ventosa; Theresa Brunet; Riccardo Berutti; Mohammad Shariati; Ali Shoeibi; Susanne A. Schneider; Alice Kuster; Matthias Baumann; David Weise; Friederike Wilbert; Wibke G. Janzarik; Matthias Eckenweiler; Volker Mall; Bernhard Haslinger; Steffen Berweck; Juliane Winkelmann; Konrad Oexle

doi:10.1002/mds.28614

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

Michael Zech, Robert Jech, Sylvia Boesch, Matej Škorvánek, Ján Necpál, Jana Švantnerová, Matias Wagner, Ariane Sadr-Nabavi, Felix Distelmaier, Martin Krenn, Tereza Serranová, Irena Rektorová, Petra Havránková, Alexandra Mosejová, Iva Příhodová, Jana Šarláková, Kristína Kulcsarová, Olga Ulmanová, Karel Bechyně, Miriam OstrozovičováVladimír Haň, Joaquim Ribeiro Ventosa, Theresa Brunet, Riccardo Berutti, Mohammad Shariati, Ali Shoeibi, Susanne A. Schneider, Alice Kuster, Matthias Baumann, David Weise, Friederike Wilbert, Wibke G. Janzarik, Matthias Eckenweiler, Volker Mall, Bernhard Haslinger, Steffen Berweck, Juliane Winkelmann, Konrad Oexle

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1959-1964
Number of pages	6
Journal	Movement Disorders
Volume	36
Issue number	8
DOIs	https://doi.org/10.1002/mds.28614
State	Published - Aug 2021

Keywords

diagnostic yield
dystonia
exome sequencing
prediction
rare disease
scoring algorithm

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Zech, M., Jech, R., Boesch, S., Škorvánek, M., Necpál, J., Švantnerová, J., Wagner, M., Sadr-Nabavi, A., Distelmaier, F., Krenn, M., Serranová, T., Rektorová, I., Havránková, P., Mosejová, A., Příhodová, I., Šarláková, J., Kulcsarová, K., Ulmanová, O., Bechyně, K., ... Oexle, K. (2021). Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study. Movement Disorders, 36(8), 1959-1964. https://doi.org/10.1002/mds.28614

@article{6546ddfe8ce04025b5c4024b292a96ab,

title = "Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study",

abstract = "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.",

keywords = "diagnostic yield, dystonia, exome sequencing, prediction, rare disease, scoring algorithm",

author = "Michael Zech and Robert Jech and Sylvia Boesch and Matej {\v S}korv{\'a}nek and J{\'a}n Necp{\'a}l and Jana {\v S}vantnerov{\'a} and Matias Wagner and Ariane Sadr-Nabavi and Felix Distelmaier and Martin Krenn and Tereza Serranov{\'a} and Irena Rektorov{\'a} and Petra Havr{\'a}nkov{\'a} and Alexandra Mosejov{\'a} and Iva P{\v r}{\'i}hodov{\'a} and Jana {\v S}arl{\'a}kov{\'a} and Krist{\'i}na Kulcsarov{\'a} and Olga Ulmanov{\'a} and Karel Bechyn{\v e} and Miriam Ostrozovi{\v c}ov{\'a} and Vladim{\'i}r Ha{\v n} and Ventosa, {Joaquim Ribeiro} and Theresa Brunet and Riccardo Berutti and Mohammad Shariati and Ali Shoeibi and Schneider, {Susanne A.} and Alice Kuster and Matthias Baumann and David Weise and Friederike Wilbert and Janzarik, {Wibke G.} and Matthias Eckenweiler and Volker Mall and Bernhard Haslinger and Steffen Berweck and Juliane Winkelmann and Konrad Oexle",

note = "Publisher Copyright: {\textcopyright} 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society",

year = "2021",

month = aug,

doi = "10.1002/mds.28614",

language = "English",

volume = "36",

pages = "1959--1964",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley & Sons Inc.",

number = "8",

}

Zech, M, Jech, R, Boesch, S, Škorvánek, M, Necpál, J, Švantnerová, J, Wagner, M, Sadr-Nabavi, A, Distelmaier, F, Krenn, M, Serranová, T, Rektorová, I, Havránková, P, Mosejová, A, Příhodová, I, Šarláková, J, Kulcsarová, K, Ulmanová, O, Bechyně, K, Ostrozovičová, M, Haň, V, Ventosa, JR, Brunet, T, Berutti, R, Shariati, M, Shoeibi, A, Schneider, SA, Kuster, A, Baumann, M, Weise, D, Wilbert, F, Janzarik, WG, Eckenweiler, M, Mall, V , Haslinger, B, Berweck, S, Winkelmann, J & Oexle, K 2021, 'Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study', Movement Disorders, vol. 36, no. 8, pp. 1959-1964. https://doi.org/10.1002/mds.28614

TY - JOUR

T1 - Scoring Algorithm-Based Genomic Testing in Dystonia

T2 - A Prospective Validation Study

AU - Zech, Michael

AU - Jech, Robert

AU - Boesch, Sylvia

AU - Škorvánek, Matej

AU - Necpál, Ján

AU - Švantnerová, Jana

AU - Wagner, Matias

AU - Sadr-Nabavi, Ariane

AU - Distelmaier, Felix

AU - Krenn, Martin

AU - Serranová, Tereza

AU - Rektorová, Irena

AU - Havránková, Petra

AU - Mosejová, Alexandra

AU - Příhodová, Iva

AU - Šarláková, Jana

AU - Kulcsarová, Kristína

AU - Ulmanová, Olga

AU - Bechyně, Karel

AU - Ostrozovičová, Miriam

AU - Haň, Vladimír

AU - Ventosa, Joaquim Ribeiro

AU - Brunet, Theresa

AU - Berutti, Riccardo

AU - Shariati, Mohammad

AU - Shoeibi, Ali

AU - Schneider, Susanne A.

AU - Kuster, Alice

AU - Baumann, Matthias

AU - Weise, David

AU - Wilbert, Friederike

AU - Janzarik, Wibke G.

AU - Eckenweiler, Matthias

AU - Mall, Volker

AU - Haslinger, Bernhard

AU - Berweck, Steffen

AU - Winkelmann, Juliane

AU - Oexle, Konrad

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

KW - diagnostic yield

KW - dystonia

KW - exome sequencing

KW - prediction

KW - rare disease

KW - scoring algorithm

UR - http://www.scopus.com/inward/record.url?scp=85105073485&partnerID=8YFLogxK

U2 - 10.1002/mds.28614

DO - 10.1002/mds.28614

M3 - Article

C2 - 33949708

AN - SCOPUS:85105073485

SN - 0885-3185

VL - 36

SP - 1959

EP - 1964

JO - Movement Disorders

JF - Movement Disorders

IS - 8

ER -

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

Abstract

Keywords

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