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Power of NGS-based tests in HSP diagnosis: analysis of massively parallel sequencing in clinical practice

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Abstract

Hereditary spastic paraplegia (HSP) refers to a group of heterogeneous neurological disorders mainly characterized by corticospinal degeneration (pure forms), but sometimes associated with additional neurological and extrapyramidal features (complex HSP). The advent of next-generation sequencing (NGS) has led to huge improvements in knowledge of HSP genetics and made it possible to clarify the genetic etiology of hundreds of “cold cases,” accelerating the process of reaching a molecular diagnosis. The different NGS-based strategies currently employed as first-tier approaches most commonly involve the use of targeted resequencing panels and exome sequencing, whereas genome sequencing remains a second-tier approach because of its high costs. The question of which approach is the best is still widely debated, and many factors affect the choice. Here, we aim to analyze the diagnostic power of different NGS techniques applied in HSP, by reviewing 38 selected studies in which different strategies were applied in different-sized cohorts of patients with genetically uncharacterized HSP.

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Acknowledgements

We thank Dr. Catherine J. Wrenn for her expert revision and editorial assistance.

Funding

The work in our laboratories is partially supported by grants from the Italian Ministry of Health (Ricerca Corrente and the 5 × 1000 voluntary contributions to FMS and AT; Ricerca Finalizzata RF-2019–12370417 to FMS; RF-2019–12370112 to AT), by the EJP-RD network “PROSPAX: an integrated multimodal progression chart in spastic ataxias” grant (project 441409627 to FMS). DG is partially supported by grants from the Fondation de l’Ataxie Charlevoix-Saguenay (www.arsacs.com) and the Cure-SPG56 program.

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  1. Arianna Scarlatti

    Present address: Laboratory of Biology, BIO@SNS, Scuola Normale Superiore, Pisa, Italy

Authors and Affiliations

  1. Molecular Medicine, IRCCS Stella Maris Foundation, Pisa, Italy

    Daniele Galatolo, Rosanna Trovato, Arianna Scarlatti, Gemma Natale, Melissa Barghigiani, Giusi Bilancieri, Filippo M. Santorelli & Alessandra Tessa

  2. UOC Neurologia, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy

    Salvatore Rossi & Gabriella Silvestri

  3. Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy

    Giovanna De Michele & Alessandro Filla

  4. Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy

    Ettore Cioffi & Carlo Casali

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Galatolo, D., Trovato, R., Scarlatti, A. et al. Power of NGS-based tests in HSP diagnosis: analysis of massively parallel sequencing in clinical practice. Neurogenetics 24, 147–160 (2023). https://doi.org/10.1007/s10048-023-00717-9

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