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Erschienen in: Current Neurology and Neuroscience Reports 3/2021

01.03.2021 | Movement Disorders (T. Simuni, Section Editor)

Genetic Dystonias: Update on Classification and New Genetic Discoveries

verfasst von: Ignacio Juan Keller Sarmiento, Niccolò Emanuele Mencacci

Erschienen in: Current Neurology and Neuroscience Reports | Ausgabe 3/2021

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Abstract

Purpose of Review

Since the advent of next-generation sequencing, the number of genes associated with dystonia has been growing exponentially. We provide here a comprehensive review of the latest genetic discoveries in the field of dystonia and discuss how the growing knowledge of biology underlying monogenic dystonias may influence and challenge current classification systems.

Recent Findings

Pathogenic variants in genes without previously confirmed roles in human disease have been identified in subjects affected by isolated or combined dystonia (KMT2B, VPS16, HPCA, KCTD17, DNAJC12, SLC18A2) and complex dystonia (SQSTM1, IRF2BPL, YY1, VPS41). Importantly, the classical distinction between isolated and combined dystonias has become harder to sustain since many genes have been shown to determine multiple dystonic presentations (e.g., ANO3, GNAL, ADCY5, and ATP1A3). In addition, a growing number of genes initially linked to other neurological phenotypes, such as developmental delay, epilepsy, or ataxia, are now recognized to cause prominent dystonia, occasionally in an isolated fashion (e.g., GNAO1, GNB1, SCN8A, RHOBTB2, and COQ8A). Finally, emerging analyses suggest biological convergence of genes linked to different dystonic phenotypes.

Summary

While our knowledge on the genetic basis of monogenic dystonias has tremendously grown, their clinical boundaries are becoming increasingly blurry. The current phenotype-based classification may not reflect the molecular structure of the disease, urging the need for new systems based on shared biological pathways among dystonia-linked genes.
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Metadaten
Titel
Genetic Dystonias: Update on Classification and New Genetic Discoveries
verfasst von
Ignacio Juan Keller Sarmiento
Niccolò Emanuele Mencacci
Publikationsdatum
01.03.2021
Verlag
Springer US
Erschienen in
Current Neurology and Neuroscience Reports / Ausgabe 3/2021
Print ISSN: 1528-4042
Elektronische ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-021-01095-1

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