C9ORF72 and UBQLN2 mutations are causes of amyotrophic lateral sclerosis in New Zealand: a genetic and pathologic study using banked human brain tissue

NEUROBIOLOGY OF AGING

卷:49

Article

Scotter, Emma L.^1,2  Smyth, Leon^1,2  Bailey, James W. T.³  Wong, Chun-Hao³  de Majo, Martina³  Vance, Caroline A.³  Synek, Beth J.⁴  Turner, Clinton⁴  Pereira, Jennifer^1,5  Charleston, Alison⁵  Waldvogel, Henry J.^1,6  Curtis, Maurice A.^1,6  Dragunowa, Mike^1,2  Shaw, Christopher E.³  Smith, Bradley N.³  Faull, Richard L. M.^1,6 

[1] Univ Auckland, Ctr Brain Res, Auckland, New Zealand

[2] Univ Auckland, Dept Pharmacol, Auckland, New Zealand

[3] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England

[4] Auckland City Hosp, LabPlus, Dept Anat Pathol, Auckland, New Zealand

[5] Auckland City Hosp, Dept Neurol, Auckland, New Zealand

[6] Univ Auckland, Dept Anat & Med Imaging, Auckland, New Zealand

关键词: Motor neurone disease;    Amyotrophic lateral sclerosis;    TARDBP;    Brain bank;    C9ORF72;    Ubiquilin;   

DOI  :  10.1016/j.neurobiolaging.2016.06.019

来源: Elsevier

【 摘 要 】

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, which causes progressive and eventually fatal loss of motor function. Here, we describe genetic and pathologic characterization 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 (DPRs), and ubiquilin. We identified 2 cases with C9ORF72 repeat expansions. Both harbored phosphorylated TDP-43 and DPR inclusions. We show that DPR inclusions can incorporate or occur independently of ubiquilin. We also identified 1 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. (C) 2016 Elsevier Inc. All rights reserved.

【 授权许可】

Free