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

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

Zech, Michael; Jech, Robert; Boesch, Sylvia; Škorvánek, Matej; Necpál, Ján; Švantnerová, Jana; Wagner, Matias; Sadr-Nabavi, Ariane; Distelmaier, Felix; Krenn, Martin; Serranová, Tereza; Rektorová, Irena; Havránková, Petra; Mosejová, Alexandra; Příhodová, Iva; Šarláková, Jana; Kulcsarová, Kristína; Ulmanová, Olga; Bechyně, Karel; Ostrozovičová, Miriam; Haň, Vladimír; Ventosa, Joaquim Ribeiro; Brunet, Theresa; Berutti, Riccardo; Shariati, Mohammad; Shoeibi, Ali; Schneider, Susanne A; Kuster, Alice...     »

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.      «

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...     »