Mutation analysis of the genes linked to early onset Alzheimer's disease and frontotemporal lobar degeneration |
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Author: | Luukkainen, Laura1,2; Helisalmi, Seppo3; Kytövuori, Laura1,2; |
Organizations: |
1Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland 2MRC, Oulu University Hospital, Oulu, Finland 3Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland
4Department of Neurology, Lapland Central Hospital, Rovaniemi, Finland
5Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland 6A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland 7Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland |
Format: | article |
Version: | accepted version |
Access: | open |
Online Access: | PDF Full Text (PDF, 0.4 MB) |
Persistent link: | http://urn.fi/urn:nbn:fi-fe2019092329299 |
Language: | English |
Published: |
IOS Press,
2019
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Publish Date: | 2019-09-23 |
Description: |
AbstractA lot of effort has been done to unravel the genetics underlying early-onset Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). However, many familial early-onset dementia (EOD) cases still show an unclear genetic background. The aim of this study was to evaluate the role of the known causative mutations and possible pathogenic variants associated with AD and FTLD in a Finnish EOD cohort. The cohort consisted of 39 patients (mean age at onset 54.8 years, range 39–65) with a positive family history of dementia or an atypical or rapidly progressive course of the disease. None of the patients carried the C9orf72 hexanucleotide repeat expansion. Mutations and variants in APP, PSEN1, PSEN2, MAPT, GRN, VCP, CHMP2B, FUS, TARDBP, TREM2, TMEM106B, UBQLN2, SOD1, PRNP, UBQLN1, and BIN1 were screened by using a targeted next generation sequencing panel. Two previously reported pathogenic mutations (PSEN1 p.His163Arg and MAPT p.Arg406Trp) were identified in the cohort. Both patients had familial dementia with an atypical early onset phenotype. In addition, a heterozygous p.Arg71Trp mutation in PSEN2 with an uncertain pathogenic nature was identified in a patient with neuropathologically confirmed AD. In conclusion, targeted investigation of the known dementia-linked genes is worthwhile in patients with onset age under 55 and a positive family history, as well as in patients with atypical features. see all
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Series: |
Journal of Alzheimer's disease |
ISSN: | 1387-2877 |
ISSN-E: | 1875-8908 |
ISSN-L: | 1387-2877 |
Volume: | 69 |
Issue: | 3 |
Pages: | 775 - 782 |
DOI: | 10.3233/JAD-181256 |
OADOI: | https://oadoi.org/10.3233/JAD-181256 |
Type of Publication: |
A1 Journal article – refereed |
Field of Science: |
3124 Neurology and psychiatry |
Subjects: | |
Funding: |
This study was supported by brain research grant from University of Oulu (LL, AMR), the Finnish Brain Foundation (ES), Academy of Finland (no 307866, MH; no 315459, AH; no 315460, AMR), and Sigrid Jusélius Foundation (MH), and the Strategic Neuroscience Funding of the University of Eastern Finland (MH; AH). |
Academy of Finland Grant Number: |
307866 315459 315460 |
Detailed Information: |
307866 (Academy of Finland Funding decision) 315459 (Academy of Finland Funding decision) 315460 (Academy of Finland Funding decision) |
Copyright information: |
© 2017 IOS Press. The Version of Record can be found at: https://doi.org/10.3233/JAD-181256. |