C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand: A genetic and pathological study using banked human brain tissue

E.L. Scotter; L. Smyth; J.W.T. Bailey; C. H. Wong; M. de Majo; C.A. Vance; B.J. Synek; C. Turner; J. Pereira; A. Charleston; H.J. Waldvogel; M.A. Curtis; M. Dragunow; C.E. Shaw; B.N. Smith; R.L.M. Faull

doi:10.1016/j.neurobiolaging.2016.06.019

C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand: A genetic and pathological study using banked human brain tissue

E.L. Scotter, L. Smyth, J.W.T. Bailey, C. H. Wong, M. de Majo, C.A. Vance, B.J. Synek, C. Turner, J. Pereira, A. Charleston, H.J. Waldvogel, M.A. Curtis, M. Dragunow, C.E. Shaw, B.N. Smith, R.L.M. Faull

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Abstract

Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease which causes progressive and eventually fatal loss of motor function. Here we describe genetic and pathological characterisation of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, University of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes, and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats and ubiquilin. We identified two cases with C9ORF72 repeat expansions. Both harboured phosphorylated TDP-43 and dipeptide repeat inclusions. We show that dipeptide repeat inclusions can incorporate or occur independently of ubiquilin. We also identified one case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This is the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.

Original language	English
Journal	Neurobiology of Aging
Early online date	5 Jul 2016
DOIs	https://doi.org/10.1016/j.neurobiolaging.2016.06.019
Publication status	E-pub ahead of print - 5 Jul 2016

Keywords

Motor neurone disease
amyotrophic lateral sclerosis
TARDBP
brain bank
C9ORF72
ubiquilin

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10.1016/j.neurobiolaging.2016.06.019

C9ORF72 and UBQLN2 are genetic_SCOTTER_Accepted 25Junel2016_GREEN AAM
© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0
Accepted author manuscript, 1.15 MBLicence: CC BY-NC-ND

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Scotter, E. L., Smyth, L., Bailey, J. W. T., Wong, C. H., de Majo, M., Vance, C. A., Synek, B. J., Turner, C., Pereira, J., Charleston, A., Waldvogel, H. J., Curtis, M. A., Dragunow, M., Shaw, C. E., Smith, B. N., & Faull, R. L. M. (2016). C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand: A genetic and pathological study using banked human brain tissue. Neurobiology of Aging. Advance online publication. https://doi.org/10.1016/j.neurobiolaging.2016.06.019

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title = "C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand: A genetic and pathological study using banked human brain tissue",

abstract = "Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease which causes progressive and eventually fatal loss of motor function. Here we describe genetic and pathological characterisation of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, University of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes, and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats and ubiquilin. We identified two cases with C9ORF72 repeat expansions. Both harboured phosphorylated TDP-43 and dipeptide repeat inclusions. We show that dipeptide repeat inclusions can incorporate or occur independently of ubiquilin. We also identified one case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This is the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.",

keywords = "Motor neurone disease, amyotrophic lateral sclerosis, TARDBP, brain bank, C9ORF72, ubiquilin",

author = "E.L. Scotter and L. Smyth and J.W.T. Bailey and Wong, {C. H.} and {de Majo}, M. and C.A. Vance and B.J. Synek and C. Turner and J. Pereira and A. Charleston and H.J. Waldvogel and M.A. Curtis and M. Dragunow and C.E. Shaw and B.N. Smith and R.L.M. Faull",

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Scotter, EL, Smyth, L , Bailey, JWT , Wong, CH , de Majo, M , Vance, CA, Synek, BJ, Turner, C, Pereira, J, Charleston, A, Waldvogel, HJ, Curtis, MA, Dragunow, M, Shaw, CE , Smith, BN & Faull, RLM 2016, 'C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand: A genetic and pathological study using banked human brain tissue', Neurobiology of Aging. https://doi.org/10.1016/j.neurobiolaging.2016.06.019

TY - JOUR

T1 - C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand

T2 - A genetic and pathological study using banked human brain tissue

AU - Scotter, E.L.

AU - Smyth, L.

AU - Bailey, J.W.T.

AU - Wong, C. H.

AU - de Majo, M.

AU - Vance, C.A.

AU - Synek, B.J.

AU - Turner, C.

AU - Pereira, J.

AU - Charleston, A.

AU - Waldvogel, H.J.

AU - Curtis, M.A.

AU - Dragunow, M.

AU - Shaw, C.E.

AU - Smith, B.N.

AU - Faull, R.L.M.

PY - 2016/7/5

Y1 - 2016/7/5

N2 - Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease which causes progressive and eventually fatal loss of motor function. Here we describe genetic and pathological characterisation of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, University of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes, and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats and ubiquilin. We identified two cases with C9ORF72 repeat expansions. Both harboured phosphorylated TDP-43 and dipeptide repeat inclusions. We show that dipeptide repeat inclusions can incorporate or occur independently of ubiquilin. We also identified one case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This is the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.

AB - Abstract Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease which causes progressive and eventually fatal loss of motor function. Here we describe genetic and pathological characterisation of brain tissue banked from 19 ALS patients over nearly 20 years at the Department of Anatomy and the Centre for Brain Research, University of Auckland, New Zealand. We screened for mutations in SOD1, TARDBP, FUS, and C9ORF72 genes, and for neuropathology caused by phosphorylated TDP-43, dipeptide repeats and ubiquilin. We identified two cases with C9ORF72 repeat expansions. Both harboured phosphorylated TDP-43 and dipeptide repeat inclusions. We show that dipeptide repeat inclusions can incorporate or occur independently of ubiquilin. We also identified one case with a UBQLN2 mutation, which showed phosphorylated TDP-43 and characteristic ubiquilin protein inclusions. This is the first study of ALS genetics in New Zealand, adding New Zealand to the growing list of countries in which C9ORF72 repeat expansion and UBQLN2 mutations are detected in ALS cases.

KW - Motor neurone disease

KW - amyotrophic lateral sclerosis

KW - TARDBP

KW - brain bank

KW - C9ORF72

KW - ubiquilin

UR - http://www.sciencedirect.com/science/article/pii/S0197458016301191

U2 - 10.1016/j.neurobiolaging.2016.06.019

DO - 10.1016/j.neurobiolaging.2016.06.019

M3 - Article

SN - 0197-4580

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

C9ORF72 and UBQLN2 are genetic causes of ALS in New Zealand: A genetic and pathological study using banked human brain tissue

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Keywords

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