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Diagnostic Yield of NGS Tests for Hereditary Ataxia: a Systematic Review

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Abstract

Next-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing hereditary ataxia (HA). Determining their diagnostic yield (DY) is crucial for optimal clinical decision-making. We conducted a comprehensive systematic literature review on the DY of NGS tests for HA. We searched PubMed and Embase databases for relevant studies between 2016 and 2022 and manually examined reference lists of relevant reviews. Eligible studies described the DY of NGS tests in patients with ataxia as a significant feature. Data from 33 eligible studies showed a median DY of 43% (IQR = 9.5–100%). The median DY for TP and ES was 46% and 41.9%, respectively. Higher DY was associated with specific phenotype selection, such as episodic ataxia at 68.35% and early and late onset of ataxia at 46.4% and 54.4%. Parental consanguinity had a DY of 52.4% (p = 0.009), and the presumed autosomal recessive (AR) inheritance pattern showed 62.5%. There was a difference between the median DY of studies that performed targeted sequencing (tandem repeat expansion, TRE) screening and those that did not (p = 0.047). A weak inverse correlation was found between DY and the extent of previous genetic investigation (rho = − 0.323; p = 0.065). The most common genes were CACNA1A and SACS. DY was higher for presumed AR inheritance pattern, positive family history, and parental consanguinity. ES appears more advantageous due to the inclusion of rare genes that might be excluded in TP.

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Funding

Renata Barreto Tenório received an MSc scholarship from the Brazilian government through CAPES-CNPq.

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Authors and Affiliations

  1. Postgraduate Program in Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Paraná, Brazil

    Renata Barreto Tenorio, Carlos Henrique F. Camargo & Hélio A.G. Teive

  2. Movement Disorders Sector, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Paraná, Brazil

    Carlos Henrique F. Camargo & Hélio A.G. Teive

  3. Medical Genetics Service, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Karina Carvalho Donis

  4. Department of Nutrition, Federal University of Paraná, Curitiba, Paraná, Brazil

    Claudia Choma Bettega Almeida

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Contributions

The authors contributed equally to the manuscript. Project conception was performed by R.B.T. and H.A.G.T. Project organization was performed by R.B.T. and C.C.B.A. Project execution and data acquisition were performed by R.B.T. and K.C.D. Data analysis and interpretation were performed by R.B.T., K.C.D. and C.H.F.C. Statistics was performed by R.B.T. and C.H.F.C. Manuscript writing was performed by R.B.T. Manuscript review and critique were performed by C.H.F.C. and H.A.G.T.

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Tenorio, R.B., Camargo, C.H.F., Donis, K.C. et al. Diagnostic Yield of NGS Tests for Hereditary Ataxia: a Systematic Review. Cerebellum (2023). https://doi.org/10.1007/s12311-023-01629-y

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