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Neurobiol Aging. 2016 Oct;46:236.e1-6. doi: 10.1016/j.neurobiolaging.2016.06.018. Epub 2016 Jul 4.

Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation.

Author information

1
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.
2
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.
3
Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
4
MRC Prion Unit, Department of Neurodegenerative Diseases, UCL Institute of Neurology, London, UK.
5
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.
6
Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Institute of Neurosciences, Hospital Clínic i Universitari de Barcelona, IDIBAPS, Barcelona, Spain.
7
Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
8
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
9
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.

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.

KEYWORDS:

CTSF; Early onset Alzheimer's disease; Exome sequencing; Homozygosity; Kufs disease; Recessive

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