eprintid: 10046640
rev_number: 22
eprint_status: archive
userid: 608
dir: disk0/10/04/66/40
datestamp: 2018-04-13 14:07:57
lastmod: 2021-10-06 22:17:10
status_changed: 2018-04-13 14:07:57
type: article
metadata_visibility: show
creators_name: Pasanen, P
creators_name: Myllykangas, L
creators_name: Pöyhönen, M
creators_name: Kiviharju, A
creators_name: Siitonen, M
creators_name: Hardy, J
creators_name: Bras, J
creators_name: Paetau, A
creators_name: Tienari, PJ
creators_name: Guerreiro, R
creators_name: Verkkoniemi-Ahola, A
title: Genetics of dementia in a Finnish cohort.
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
keywords: Disease genetics, DNA sequencing
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2018-02-23
date_type: published
official_url: http://dx.doi.org/10.1038/s41431-018-0117-3
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1539983
doi: 10.1038/s41431-018-0117-3
pii: 10.1038/s41431-018-0117-3
language_elements: eng
lyricists_name: Hardy, John
lyricists_name: Louro Guerreiro, Rita
lyricists_name: Smalley, June
lyricists_name: Tomas Bras, Jose
lyricists_id: JHARD28
lyricists_id: RJLOU51
lyricists_id: JASMA87
lyricists_id: JMTOM86
actors_name: Tomas Bras, Jose
actors_id: JMTOM86
actors_role: owner
full_text_status: public
publication: Eur J Hum Genet
event_location: England
issn: 1476-5438
citation:        Pasanen, P;    Myllykangas, L;    Pöyhönen, M;    Kiviharju, A;    Siitonen, M;    Hardy, J;    Bras, J;                 ... Verkkoniemi-Ahola, A; + view all <#>        Pasanen, P;  Myllykangas, L;  Pöyhönen, M;  Kiviharju, A;  Siitonen, M;  Hardy, J;  Bras, J;  Paetau, A;  Tienari, PJ;  Guerreiro, R;  Verkkoniemi-Ahola, A;   - view fewer <#>    (2018)    Genetics of dementia in a Finnish cohort.                   Eur J Hum Genet        10.1038/s41431-018-0117-3 <https://doi.org/10.1038/s41431-018-0117-3>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10046640/1/Genetics_dementia_Finnish_accepted.pdf