title: Mutation Frequency of the Major Frontotemporal Dementia Genes, MAPT, GRN and C9ORF72 in a Turkish Cohort of Dementia Patients.
abstract: 'Microtubule-associated protein tau' (MAPT), 'granulin' (GRN) and 'chromosome 9 open reading frame72' (C9ORF72) gene mutations are the major known genetic causes of frontotemporal dementia (FTD). Recent studies suggest that mutations in these genes may also be associated with other forms of dementia. Therefore we investigated whether MAPT, GRN and C9ORF72 gene mutations are major contributors to dementia in a random, unselected Turkish cohort of dementia patients. A combination of whole-exome sequencing, Sanger sequencing and fragment analysis/Southern blot was performed in order to identify pathogenic mutations and novel variants in these genes as well as other FTD-related genes such as the 'charged multivesicular body protein 2B' (CHMP2B), the 'FUS RNA binding protein' (FUS), the 'TAR DNA binding protein' (TARDBP), the 'sequestosome1' (SQSTM1), and the 'valosin containing protein' (VCP). We determined one pathogenic MAPT mutation (c.1906C>T, p.P636L) and one novel missense variant (c.38A>G, p.D13G). In GRN we identified a probably pathogenic TGAG deletion in the splice donor site of exon 6. Three patients were found to carry the GGGGCC expansions in the non-coding region of the C9ORF72 gene. In summary, a complete screening for mutations in MAPT, GRN and C9ORF72 genes revealed a frequency of 5.4% of pathogenic mutations in a random cohort of 93 Turkish index patients with dementia.
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Gamze
authors.initials: G
authors.lastname: Guven
authors.affiliation: Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.|Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.|Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Jose
authors.initials: J
authors.lastname: Bras
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.affiliation: Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Gurvit
authors.affiliation: Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Basar
authors.initials: B
authors.lastname: Bilgic
authors.affiliation: Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Hasmet
authors.initials: H
authors.lastname: Hanagasi
authors.affiliation: DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rizzu
authors.affiliation: Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.affiliation: Behavioural Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Emre
authors.affiliation: Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel-Unaltuna
authors.affiliation: Institute of Human Genetics, University of Ulm, Ulm, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Just
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.|Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Guerreiro
mesh_terms: D015139:Blotting, Southern; D000073885:C9orf72 Protein; D015331:Cohort Studies; D059472:Exome; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D000077153:Progranulins; D011506:Proteins / Q000235:genetics*; D014421:Turkey; D016875:tau Proteins / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D011506:Proteins; D016875:tau Proteins