Repository logo
 
Publication

Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE

2020-12Journal article Open access
Simple item page
dc.contributor.authorGromicho, M
dc.contributor.authorCoutinho, AM
dc.contributor.authorPronto-Laborinho, AC
dc.contributor.authorRaposeiro, R
dc.contributor.authorTavares, J
dc.contributor.authorAntunes, D
dc.contributor.authorde Carvalho, M
dc.date.accessioned2021-06-23T14:45:06Z
dc.date.available2021-06-23T14:45:06Z
dc.date.issued2020-12
dc.description.abstractAmyotrophic 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Neurol. 2020;267(12):3578-3592pt_PT
dc.identifier.doi10.1007/s00415-020-10042-ypt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3744
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_PT
dc.subjectC9orf72 Proteinpt_PT
dc.subjectDNA Repeat Expansionpt_PT
dc.subjectHigh-Throughput Nucleotide Sequencingpt_PT
dc.subjectHumanspt_PT
dc.subjectPortugalpt_PT
dc.subjectAmyotrophic Lateral Sclerosispt_PT
dc.subjectFrontotemporal Dementiapt_PT
dc.subjectNeurodegenerative Diseasespt_PT
dc.subjectHDE GENpt_PT
dc.titleTargeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HREpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage3592pt_PT
oaire.citation.issue12pt_PT
oaire.citation.startPage3578pt_PT
oaire.citation.titleJournal of neurologypt_PT
oaire.citation.volume267pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
J Neurology 2020_267_3578.pdf
Size:
764.38 KB
Format:
Adobe Portable Document Format
Download

Collections

GEN - Artigos