Mutation Analysis of the Genes Linked to Early Onset Alzheimer's Disease and Frontotemporal Lobar Degeneration
| Autor: | Seppo Helisalmi, Mikko Hiltunen, Anne M. Remes, Johanna Krüger, Riitta Ahmasalo, Laura Kytövuori, Annakaisa Haapasalo, Laura Luukkainen, Eino Solje |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male DNA Mutational Analysis tau Proteins Bioinformatics TARDBP Cohort Studies 03 medical and health sciences 0302 clinical medicine C9orf72 Alzheimer Disease mental disorders PSEN2 Presenilin-2 PSEN1 Presenilin-1 Medicine Dementia Humans Early-onset Alzheimer's disease Cognitive Dysfunction Age of Onset Finland Aged business.industry General Neuroscience General Medicine Frontotemporal lobar degeneration Middle Aged medicine.disease Causality Psychiatry and Mental health Clinical Psychology 030104 developmental biology Phenotype Disease Progression Female Geriatrics and Gerontology Frontotemporal Lobar Degeneration business 030217 neurology & neurosurgery Frontotemporal dementia |
| Zdroj: | Journal of Alzheimer's disease : JAD. 69(3) |
| ISSN: | 1875-8908 |
| Popis: | A 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. |
| Databáze: | OpenAIRE |
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