Whole exome sequencing and clinical investigation of young onset dystonia: What can we learn?

Abstract

BACKGROUND:

Dystonia is a heterogeneous movement disorder involving various genetic backgrounds, and the implication of whole exome sequencing (WES) has yet to be clearly elucidated. In this study, we performed WES in Korean patients with young-onset dystonia.

METHODS:

We recruited patients with young-onset dystonia based on the new MDS dystonia classification at Samsung Medical Centre from 2015 to 2019. We excluded subjects diagnosed by single gene tests (GCH1, TOR1A, PANK2, PRRT2, and SGCE) or levodopa trials and subjects with focal or possible secondary dystonia. We performed WES in all enrolled subjects and confirmed the results with Sanger sequencing.

RESULTS:

Of the 43 patients, we detected 11 disease-causing variants, classified as either pathogenic or likely pathogenic, in 9 patients (20.9%). Generalized dystonia, infancy-childhood-onset dystonia, and other combined neurologic manifestations were related with PV/LPV. When we retrospectively reviewed the patients with PV/LPV, brain imaging was diagnostic in 3 subjects (HTRA1, SCL20A, and WDR45), clinical characteristics of paroxysmal presentation were observed in 2 (ADCY5 and ATP1A3), and microcephaly was noted in 1 patient (KMT2B).

CONCLUSION:

Clinical exome sequencing is helpful for the diagnosis of dystonia, especially for that with infancy-childhood onset, and generalized dystonia with other neurologic manifestations. Additionally, careful evaluations and examinations could provide information for selecting candidates for genetic testing.

• Authors: Jong Hyeon Ahn, Ah Reum Kim, Woong-Yang Park, Jin Whan Cho, Jongkyu Park, Jinyoung Youn
• Journal: Parkinsonism & related disorders (Parkinsonism Relat Disord) Vol. 115 Pg. 105814 (10 2023) ISSN: 1873-5126 [Electronic] England
• PMID: 37607452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier Ltd. All rights reserved.

Chemical References

• TOR1A protein, human
• Molecular Chaperones
• ATP1A3 protein, human
• Sodium-Potassium-Exchanging ATPase
• WDR45 protein, human
• Carrier Proteins

Topics

• Humans
• Child
• Dystonia (diagnosis, genetics)
• Exome Sequencing
• Retrospective Studies
• Dystonic Disorders (diagnosis, genetics)
• Genetic Testing
• Mutation (genetics)
• Molecular Chaperones (genetics)
• Sodium-Potassium-Exchanging ATPase (genetics)
• Carrier Proteins (genetics)