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Review
. 2021 Mar 23:12:638730.
doi: 10.3389/fgene.2021.638730. eCollection 2021.

The History of Gene Hunting in Hereditary Spinocerebellar Degeneration: Lessons From the Past and Future Perspectives

Ashraf Yahia  1   2   3   4 , Giovanni Stevanin  3   4
Affiliations
Review

The History of Gene Hunting in Hereditary Spinocerebellar Degeneration: Lessons From the Past and Future Perspectives

Ashraf Yahia et al. Front Genet. .

Abstract

Hereditary spinocerebellar degeneration (SCD) encompasses an expanding list of rare diseases with a broad clinical and genetic heterogeneity, complicating their diagnosis and management in daily clinical practice. Correct diagnosis is a pillar for precision medicine, a branch of medicine that promises to flourish with the progressive improvements in studying the human genome. Discovering the genes causing novel Mendelian phenotypes contributes to precision medicine by diagnosing subsets of patients with previously undiagnosed conditions, guiding the management of these patients and their families, and enabling the discovery of more causes of Mendelian diseases. This new knowledge provides insight into the biological processes involved in health and disease, including the more common complex disorders. This review discusses the evolution of the clinical and genetic approaches used to diagnose hereditary SCD and the potential of new tools for future discoveries.

Keywords: diagnosis; gene discovery; hereditary cerebellar ataxia; hereditary spastic paraplegia; neurogenetics; spinocerebellar ataxia; spinocerebellar degeneration.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Methods used in diagnosing novel subtypes of hereditary spinocerebellar degeneration (SCD). Filled circles represent the methods used in identifying SCD subtypes, and the bar chart shows the number of SCD subtypes identified by each method or combination of methods. Empty circles represent the unused methods. SCD, hereditary spinocerebellar degeneration; WES, whole-exome sequencing; NGS, next-generation sequencing; and WGS, whole-genome sequencing.
Figure 2
Figure 2
Cumulative evolution of the number of subtypes of hereditary SCD identified per year.
Figure 3
Figure 3
The strengths and weaknesses of the methods used in diagnosing subtypes of hereditary SCD. WES, whole-exome sequencing; WGS, whole-genome sequencing; Targeted approaches, targeted next-generation sequencing, candidate gene approaches, and repeats expansion detection methods; SNPs, single nucleotide polymorphisms; and CNVs, copy number variations.
See this image and copyright information in PMC

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