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07.07.2020 | Original Communication

Targeted next-generation sequencing study in familial ALS-FTD Portuguese patients negative for C9orf72 HRE

verfasst von: Marta Gromicho, Ana Margarida Coutinho, Ana Catarina Pronto-Laborinho, Rita Raposeiro, Joana Tavares, Diana Antunes, Mamede de Carvalho

Erschienen in: Journal of Neurology | Ausgabe 12/2020

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Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with clinical and etiological heterogeneity and a complex genetic contribution. Clinical, neuropathological, and genetic evidence revealed that ALS and frontotemporal dementia (FTD) are in part of a single disease continuum. Genetic causes have been identified in sporadic (SALS) and familial patients (FALS) and the recurrent genetic factor underlying ALS and FTD is the C9orf72 hexanucleotide repeat expansion (HRE). However, in our population, the concomitance of ALS and FTD cannot be explained by C9orf72 HRE in many FALS and SALS cases. Our aim is to further understand the genetic basis of ALS in Portuguese patients. 34 patients with FALS or SALS-FTD, negative for C9orf72 HRE, were screened for rare variants in a panel of 29 relevant genes by next-generation sequencing. We detected 15 variants in 11 genes, one classified as pathogenic in TARDBP, two as likely pathogenic in TARDBP and PRPH, and the others as variants of unknown significance (VUS). Gene variants, including VUS, were found in 41.2% FALS patients and 40% SALS-FTD. In most patients, no potential pathogenic variants were found. Our results emphasize the need to enhance the efforts to unravel the genetic architecture of ALS-FTD.

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Titel: Targeted next-generation sequencing study in familial ALS-FTD Portuguese patients negative for C9orf72 HRE
verfasst von: Marta Gromicho
Ana Margarida Coutinho
Ana Catarina Pronto-Laborinho
Rita Raposeiro
Joana Tavares
Diana Antunes
Mamede de Carvalho
Publikationsdatum: 07.07.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 12/2020
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-020-10042-y

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