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Eur J Hum Genet. 2018 Jun;26(6):827-837. doi: 10.1038/s41431-018-0117-3. Epub 2018 Feb 23.

Genetics of dementia in a Finnish cohort.

Author information

1
Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland. petra.pasanen@utu.fi.
2
Tyks Genetics and Saske, Department of Medical Genetics, Turku University Hospital, Turku, Finland. petra.pasanen@utu.fi.
3
Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
4
Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland.
5
Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
6
Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
7
Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
8
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
9
UK Dementia Research Institute at UCL, London, UK.
10
Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193, Aveiro, Portugal.
11
Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Abstract

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias. Variants in APP, PSEN1 and PSEN2 are typically linked to early-onset AD, and several genetic risk loci are associated with late-onset AD. Inherited FTD can be caused by hexanucleotide expansions in C9orf72, or variants in GRN, MAPT or CHMP2B. Several other genes have also been linked to FTD or FTD with motor neuron disease. Here we describe a cohort of 60 Finnish families with possible inherited dementia. Our aim was to clarify the genetic background of dementia in this cohort by analysing both known dementia-associated genes (APOE, APP, C9ORF72, GRN, PSEN1 and PSEN2) and searching for rare or novel segregating variants with exome sequencing. C9orf72 repeat expansions were detected in 12 (20%) of the 60 families, including, in addition to FTD, a family with neuropathologically verified AD. Twelve families (10 with AD and 2 with FTD) with representative samples from affected and unaffected subjects and without C9orf72 expansions were selected for whole-exome sequencing. Exome sequencing did not reveal any variants that could be regarded unequivocally causative, but revealed potentially damaging variants in UNC13C and MARCH4.

PMID:
29476165
PMCID:
PMC5974394
DOI:
10.1038/s41431-018-0117-3
[Indexed for MEDLINE]
Free PMC Article

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