Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies

Celia Kun-Rodrigues; Owen A Ross; Tatiana Orme; Claire Shepherd; Laura Parkkinen; Lee Darwent; Dena Hernandez; Olaf Ansorge; Lorraine N Clark; Lawrence S Honig; Karen Marder; Afina Lemstra; Philippe Scheltens; Wiesje van der Flier; Eva Louwersheimer; Henne Holstege; Ekaterina Rogaeva; Peter St George-Hyslop; Elisabet Londos; Henrik Zetterberg; Imelda Barber; Anne Braae; Kristelle Brown; Kevin Morgan; Walter Maetzler; Daniela Berg; Claire Troakes; Safa Al-Sarraj; Tammaryn Lashley; Janice Holton; Yaroslau Compta; Vivianna Van Deerlin; John Q Trojanowski; Geidy E Serrano; Thomas G Beach; Jordi Clarimon; Alberto Lleó; Estrella Morenas-Rodríguez; Suzanne Lesage; Douglas Galasko; Eliezer Masliah; Isabel Santana; Monica Diez; Pau Pastor; Pentti J Tienari; Liisa Myllykangas; Minna Oinas; Tamas Revesz; Andrew Lees; Brad F Boeve; Ronald C Petersen; Tanis J Ferman; Valentina Escott-Price; Neill Graff-Radford; Nigel J Cairns; John C Morris; David J Stone; Stuart Pickering-Brown; David Mann; Dennis W Dickson; Glenda M Halliday; Andrew Singleton; Rita Guerreiro; Jose Bras

doi:10.1016/j.neurobiolaging.2016.08.023

Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies

Neurobiol Aging. 2017 Jan:49:214.e13-214.e15. doi: 10.1016/j.neurobiolaging.2016.08.023. Epub 2016 Sep 2.

Authors

Celia Kun-Rodrigues¹, Owen A Ross², Tatiana Orme¹, Claire Shepherd³, Laura Parkkinen⁴, Lee Darwent¹, Dena Hernandez⁵, Olaf Ansorge⁴, Lorraine N Clark⁶, Lawrence S Honig⁶, Karen Marder⁶, Afina Lemstra⁷, Philippe Scheltens⁷, Wiesje van der Flier⁷, Eva Louwersheimer⁷, Henne Holstege⁷, Ekaterina Rogaeva⁸, Peter St George-Hyslop⁸, Elisabet Londos⁹, Henrik Zetterberg¹⁰, Imelda Barber¹¹, Anne Braae¹¹, Kristelle Brown¹¹, Kevin Morgan¹¹, Walter Maetzler¹², Daniela Berg¹², Claire Troakes¹³, Safa Al-Sarraj¹³, Tammaryn Lashley¹⁴, Janice Holton¹⁴, Yaroslau Compta¹⁵, Vivianna Van Deerlin¹⁶, John Q Trojanowski¹⁶, Geidy E Serrano¹⁷, Thomas G Beach¹⁷, Jordi Clarimon¹⁸, Alberto Lleó¹⁸, Estrella Morenas-Rodríguez¹⁸, Suzanne Lesage¹⁹, Douglas Galasko²⁰, Eliezer Masliah²⁰, Isabel Santana²¹, Monica Diez²², Pau Pastor²², Pentti J Tienari²³, Liisa Myllykangas²⁴, Minna Oinas²⁵, Tamas Revesz¹⁴, Andrew Lees¹⁴, Brad F Boeve²⁶, Ronald C Petersen²⁶, Tanis J Ferman²⁷, Valentina Escott-Price²⁸, Neill Graff-Radford²⁹, Nigel J Cairns³⁰, John C Morris³⁰, David J Stone³¹, Stuart Pickering-Brown³², David Mann³², Dennis W Dickson², Glenda M Halliday³, Andrew Singleton⁵, Rita Guerreiro³³, Jose Bras³⁴

Affiliations

¹ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
² Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
³ Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
⁴ Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
⁵ Laboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, MD, USA.
⁶ Taub Institute for Alzheimer Disease and the Aging Brain, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
⁷ Department of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
⁸ Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
⁹ Clinical Memory Research Unit, Institution of Clinical Sciences Malmö, Lund University, Lund, Sweden.
¹⁰ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹¹ Translation Cell Sciences-Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
¹² Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, Tuebingen, Germany; Department of Neurology, Christian-Albrechts University of Kiel, Kiel, Germany.
¹³ Department of Basic and Clinical Neuroscience and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
¹⁴ Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
¹⁵ Movement Disorders Unit, Neurology Service, Clinical Neuroscience Institute (ICN), Hospital Clínic, University of Barcelona, IDIBAPS, Barcelona, Spain.
¹⁶ Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹⁷ Banner Sun Health Research Institute, Sun City, AZ, USA.
¹⁸ Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universidad Autònoma de Barcelona, Barcelona, Catalonia, Spain.
¹⁹ Sorbonne Université, Université Pierre et Marie Curie-Paris 06, Inserm, Centre National de la Reserche Scientifique, Institute du Cerveau et de la Moelle épinière, Paris, France; Assistance Publique Hôpitaux de Paris, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France.
²⁰ Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.
²¹ Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
²² Memory Unit, Department of Neurology, University Hospital Mútua de Terrassa, and Foundation Mútua de Terrassa, Barcelona, Spain; Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
²³ Molecular Neurology, Research Programs Unit, University of Helsinki, Department of Neurology, Helsinki University Hospital, Helsinki, Finland.
²⁴ Department of Pathology, University of Helsinki, Helsinki, Finland and HUSLAB.
²⁵ Department of Neuropathology and Neurosurgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
²⁶ Neurology Department, Mayo Clinic, Rochester, MN, USA.
²⁷ Department of Psychiatry, Mayo Clinic, Jacksonville, FL, USA; Department of Psychology, Mayo Clinic, Jacksonville, FL, USA.
²⁸ MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
²⁹ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
³⁰ Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
³¹ Genetics and Pharmacogenomics, Merck Research Laboratories, West Point, PA, USA.
³² Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
³³ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Department of Medical Sciences and Institute of Biomedicine-iBiMED, University of Aveiro, Aveiro, Portugal.
³⁴ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Department of Medical Sciences and Institute of Biomedicine-iBiMED, University of Aveiro, Aveiro, Portugal. Electronic address: j.bras@ucl.ac.uk.

PMID: 27666590
PMCID: PMC5154872
DOI: 10.1016/j.neurobiolaging.2016.08.023

Abstract

C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB.

Keywords: C9orf72; Dementia with Lewy bodies (DLB); Genetic screen.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

C9orf72 Protein / genetics*
Cohort Studies
DNA Repeat Expansion / genetics*
Genetic Association Studies*
Humans
Lewy Body Disease / genetics*

Substances

C9orf72 Protein
C9orf72 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding