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Open Access 01-03-2019 | Spastic Paraplegia | Original Article

Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes

Authors: Ewelina Elert-Dobkowska, Iwona Stepniak, Wioletta Krysa, Karolina Ziora-Jakutowicz, Maria Rakowicz, Anna Sobanska, Jacek Pilch, Dorota Antczak-Marach, Jacek Zaremba, Anna Sulek

Published in: Neurogenetics | Issue 1/2019

Abstract

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Numerous genes linked to HSPs, overlapping phenotypes between HSP subtypes and other neurodegenerative disorders and the HSPs’ dual mode of inheritance (both dominant and recessive) make the genetic diagnosis of HSPs complex and difficult. Out of the original HSP cohort comprising 306 index cases (familial and isolated) who had been tested according to “traditional workflow/guidelines” by Multiplex Ligation-dependent Probe Amplification (MLPA) and Sanger sequencing, 30 unrelated patients (all familial cases) with unsolved genetic diagnoses were tested using next-generation sequencing (NGS). One hundred thirty-two genes associated with spastic paraplegias, hereditary ataxias and related movement disorders were analysed using the Illumina TruSight™ One Sequencing Panel. The targeted NGS data showed pathogenic variants, likely pathogenic variants and those of uncertain significance (VUS) in the following genes: SPAST (spastin, SPG4), ATL1 (atlastin 1, SPG3), WASHC5 (SPG8), KIF5A (SPG10), KIF1A (SPG30), SPG11 (spatacsin), CYP27A1, SETX and ITPR1. Out of the nine genes mentioned above, three have not been directly associated with the HSP phenotype to date. Considering the phenotypic overlap and joint cellular pathways of the HSP, spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis (ALS) genes, our findings provide further evidence that common genetic testing may improve the diagnostics of movement disorders with a spectrum of ataxia-spasticity signs.

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Title: Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes
Authors: Ewelina Elert-Dobkowska
Iwona Stepniak
Wioletta Krysa
Karolina Ziora-Jakutowicz
Maria Rakowicz
Anna Sobanska
Jacek Pilch
Dorota Antczak-Marach
Jacek Zaremba
Anna Sulek
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Keywords: Spastic Paraplegia
Amyotrophic Lateral Sclerosis
Movement Disorder
Spinocerebellar Ataxia
Published in: Neurogenetics / Issue 1/2019
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-019-00565-6

At a glance: The STEP trials

Springer Medicine

Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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