Genetics of Dominant Ataxias

Yahia, Ashraf; Stevanin, Giovanni

doi:10.1007/978-3-031-24345-5_4

Ashraf Yahia^6,7 &
Giovanni Stevanin^7,8

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

380 Accesses

Abstract

Autosomal dominant cerebellar ataxia (ADCA) accounts for more than fifty inherited neurological diseases caused by various underlying mechanisms leading to progressive or intermittent phenotypes. Most ADCAs develop due to alterations in signal transduction, ion homeostasis, or pathological DNA expansions. Yet, other pathological mechanisms can directly or indirectly contribute to the development of these diseases. Initially, ADCA diagnosis was dominated by linkage and nucleotide repeat expansion analyses. However, the advent of next-generation sequencing has enhanced ADCA diagnosis, including the discovery of novel forms due to nucleotide repeat expansions and conventional mutations, with limited reliable genotype–phenotype correlations within the major ADCA subgroups. The developments in ADCA diagnosis have outpaced the discovery of effective treatments and biomarkers for these diseases, particularly the progressive neurodegenerative subtypes. Multiple clinical trials are, however, underway with some promising results but there are still many challenges to overcome.

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Abbreviations

ADCA:: Autosomal dominant cerebellar ataxia
ADCADN:: Autosomal dominant cerebellar ataxia, deafness, and narcolepsy
CAPOS:: Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss
CNV:: Copy number variation
DHA:: Docosahexaenoic acid
DRPLA:: Dentatorubral-pallidoluysian atrophy
EA:: Episodic ataxia
EEAT1:: Excitatory amino acid transporter-1
EGFR:: Epidermal growth factor receptor
ER:: Endoplasmic reticulum
NGS:: Next-generation sequencing
NMDA:: N-methyl-D-aspartate
NPTX1:: Neuronal pentraxin 1 protein/gene
RAN:: Repeat-associated non-AUG
SCA:: Spinocerebellar ataxia
SCA42ND:: SCA42 with neurodevelopmental deficits
SPTBN2:: Spectrin beta non-erythrocytic-2 protein
UTR:: Untranslated region
WES:: Whole exome sequencing
WGS:: Whole genome sequencing

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Acknowledgments

We are grateful to Alexis Brice and Nick Barton for critical reading of the manuscript.

Funding

The authors’ work is financially supported by ATAXIA-UK (to GS), the European Union’s Horizon 2020 research and innovation program under grant agreement No. 779257 (to GS), and the association Connaître les Syndromes Cérébelleux (to GS).

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Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum, Sudan
Ashraf Yahia
Institut du Cerveau – Paris Brain Institute, ICM, Sorbonne University, INSERM, CNRS, APHP, Paris, France
Ashraf Yahia & Giovanni Stevanin
INCIA, CNRS, Bordeaux University, EPHE, Bordeaux, France
Giovanni Stevanin

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Professor of Neurology, Shuang Ho Hospital, Taipei Medical University, Taipei, (Republic of China), Taiwan
Bing-wen Soong
Professor of Neuroanatomy, University of Mons and CHU-Charleroi, Charleroi, Belgium
Mario Manto
Paris Brain Institute, (Institut du Cerveau – ICM), CNRS INSERM, Sorbonne Université, APHP, Paris, France
Alexis Brice
Department of Neurology, Spencer Fox Eccles School of Medicine University of Utah, Salt Lake City, UT, USA
Stefan M. Pulst

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Yahia, A., Stevanin, G. (2023). Genetics of Dominant Ataxias. In: Soong, Bw., Manto, M., Brice, A., Pulst, S.M. (eds) Trials for Cerebellar Ataxias. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-031-24345-5_4

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