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

Publication date: Available online 5 July 2016
Source:Neurobiology of Aging
Author(s): 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
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.



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