Author/Editor		Zalar, Bojan; Maver, Aleš; Kovanda, Ana; Peterlin, Ana; Peterlin, Borut
Title		Clinical exome sequencing in dementias
Type		članek
Vol. and No.		Letnik 30, št. 2
Publication year		2018
Volume		str. 216-219
ISSN		0353-5053 - Psychiatria Danubina
Language		eng
Abstract		Background: Dementias are clinically and genetically heterogeneous group of neurodegenerative disorders. Often, dementias with genetic etiology are clinically indistinguishable from non-genetic ones. The aim of this retrospective study was to evalua te the yield of clinical exome sequencing in dementias, potentially associated with monogenic genetic predisposition. Subjects and methods: For this purpose 20 consecutive patients younger than 65 years were studied in the period from January 2014 to December 2017; 14 with the diagnosis of Frontotemporal dementia (FTD), 3 with early-onset Alzheimer disease (EOAD) and 3 with unspecified dementia. In addition to clinical exome sequencing including 57 genes associated with dementia, C9orf72 hexanucleotide expansion as tested in all patients. Results: We found genetic etiology in 6 patients: 2 mutations in the PSEN1 gene (p.Pro264Ser and p.Phe105Cys) in the EOAD patients, C9orf72 expansion and MAPT (c.1920+16C>T), mutation in the FTD group of patients as well as MAPT (c.1920+16C>T) mutation and likely pathogenic mutation in the TYROBP mutation (p.Asp32Asn) in patients with unspecified diagnosis. Conclusions: Our preliminary results imply significant diagnostic yield in identifying rare genetic causes of dementia, combining comprehensive clinical exome sequencing and targeted C9orf72 expansion testing.
Keywords		dementia early-onset dementia Alzheimer's disease demenca zgodnja demenca Alzheimerjeva bolezen