Journal article

CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral sclerosis

Carol Dobson-Stone, Marianne Hallupp, Hamideh Shahheydari, Audrey MG Ragagnin, Zac Chatterton, Francine Carew-Jones, Claire E Shepherd, Holly Stefen, Esmeralda Paric, Thomas Fath, Elizabeth M Thompson, Peter Blumbergs, Cathy L Short, Colin D Field, Peter K Panegyres, Jane Hecker, Garth Nicholson, Alex D Shaw, Janice M Fullerton, Agnes A Luty Show all

Brain | OXFORD UNIV PRESS | Published : 2020

Abstract

Frontotemporal dementia and amyotrophic lateral sclerosis are clinically and pathologically overlapping disorders with shared genetic causes. We previously identified a disease locus on chromosome 16p12.1-q12.2 with genome-wide significant linkage in a large European Australian family with autosomal dominant inheritance of frontotemporal dementia and amyotrophic lateral sclerosis and no mutation in known amyotrophic lateral sclerosis or dementia genes. Here we demonstrate the segregation of a novel missense variant in CYLD (c.2155A>G, p.M719V) within the linkage region as the genetic cause of disease in this family. Immunohistochemical analysis of brain tissue from two CYLD p.M719V mutation ..

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Awarded by Dementia Research Team Grant


Awarded by NHMRC


Awarded by NHMRC Boosting Dementia Research Leadership Fellowship


Awarded by Australian Research Council


Awarded by Wellcome Trust


Awarded by UK Department of Health under the Health Innovation Challenge Fund


Awarded by US National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS)


Funding Acknowledgements

This research was funded by the National Health and Medical Research Council of Australia (NHMRC) Project Grants 1062539 (to C.D.S. and J.B.K.), 1140708 (to C.D.S., J.B.K., I.P.B. and J.D.A.) and 1083209 (to T.F.), and Dementia Research Team Grant 1095215 (to I.P.B., J.D.A., J.B.K., C.D.S.) and by funding to ForeFront, a collaborative research group dedicated to the study of FTD and MND, from the NHMRC (1037746, 1095127, 1132524). C.D.S. is funded by an NHMRC Boosting Dementia Research Leadership Fellowship (1138223) and the University of Sydney. T.F. is supported by an Australian Research Council Discovery Project Grant (180101473). J.M.F. and A.D.S. were supported by NHMRC Project Grant 1063960 (to J.M.F. and P.R.S.), and J.M.F. was additionally supported by the Janette Mary O'Neil Research Fellowship. N.R. is funded by a Wellcome Trust Intermediate Clinical Fellowship (WT097163MA), the Wellcome Trust and UK Department of Health under the Health Innovation Challenge Fund (100935/Z/13/Z), the Newcastle NIHR Biomedical Research Centre (BRC) and the Newcastle MRC/EPSRC Molecular Pathology Node. M.F.B. and M.B. were supported by the Victorian Government's Operational Infrastructure Support Program and the NHMRC Independent Research Institute Infrastructure Support Scheme. M.B. was also supported by NHMRC Program Grant (1054618) and NHMRC Senior Research Fellowship (1102971). Funding was provided to J.E.L. by US National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) (R01NS073873) and the American ALS Association. O.P. is supported by an NHMRC Senior Research Fellowship (1103258). G.M.H. holds an NHMRC Senior Principal Research Fellowship (1079679). K.L.W. was supported by a University of Sydney Postgraduate Scholarship during this research.