title: Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation.
abstract: We have previously reported the whole genome genotyping analysis of 2 consanguineous siblings clinically diagnosed with early onset Alzheimer's disease (AD). In this analysis, we identified several large regions of homozygosity shared between both affected siblings, which we suggested could be candidate loci for a recessive genetic lesion underlying the early onset AD in these cases. We have now performed exome sequencing in one of these siblings and identified the potential cause of disease: the CTSF c.1243G>A:p.Gly415Arg mutation in homozygosity. Biallelic mutations in this gene have been shown to cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis with some cases resembling the impairment seen in AD.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK; Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal.
authors.forename: Jose
authors.initials: J
authors.lastname: Bras
authors.affiliation: Department of Neurology, Rabin Medical Center, Beilinson Campus, and Felsenstein Research Center, Petah Tiqva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Djaldetti
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Alves
authors.affiliation: MRC Prion Unit, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Mead
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Darwent
authors.affiliation: Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERNED, Center for Networked Biomedical Research into Neurodegenerative Diseases, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleo
authors.affiliation: Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Institute of Neurosciences, Hospital Clínic i Universitari de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Molinuevo
authors.affiliation: Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimon
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK; Department of Medical Sciences and Institute of Biomedicine - iBiMED, University of Aveiro, Aveiro, Portugal. Electronic address: r.guerreiro@ucl.ac.uk.
authors.forename: Rita
authors.initials: R
authors.lastname: Guerreiro
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D056646:Cathepsin F / Q000235:genetics*; D003241:Consanguinity; D059472:Exome / Q000235:genetics*; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics; D017421:Sequence Analysis; D035781:Siblings
chemical_list: C534090:CTSF protein, human; D056646:Cathepsin F
keywords: CTSF; Early onset Alzheimer's disease; Exome sequencing; Homozygosity; Kufs disease; Recessive