TY - JOUR
T1 - Genetic overlap between dystonia and other neurologic disorders
T2 - A study of 1,100 exomes
AU - Dzinovic, Ivana
AU - Boesch, Sylvia
AU - Škorvánek, Matej
AU - Necpál, Ján
AU - Švantnerová, Jana
AU - Pavelekova, Petra
AU - Havránková, Petra
AU - Tsoma, Eugenia
AU - Indelicato, Elisabetta
AU - Runkel, Eva
AU - Held, Valentin
AU - Weise, David
AU - Janzarik, Wibke
AU - Eckenweiler, Matthias
AU - Berweck, Steffen
AU - Mall, Volker
AU - Haslinger, Bernhard
AU - Jech, Robert
AU - Winkelmann, Juliane
AU - Zech, Michael
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/9
Y1 - 2022/9
N2 - Introduction: Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia. Methods: Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability. Results: Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia. Conclusions: Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations.
AB - Introduction: Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia. Methods: Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability. Results: Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia. Conclusions: Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations.
KW - Dystonia
KW - Exome sequencing
KW - Molecular overlap
KW - Panel
KW - Shared genes
UR - https://www.scopus.com/pages/publications/85134757430
U2 - 10.1016/j.parkreldis.2022.07.003
DO - 10.1016/j.parkreldis.2022.07.003
M3 - Article
C2 - 35872528
AN - SCOPUS:85134757430
SN - 1353-8020
VL - 102
SP - 1
EP - 6
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -