The analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism

NEUROBIOLOGY OF AGING

卷:36

Article

Schottlaender, Lucia V.¹  Polke, James M.^1,2  Ling, Helen^1,3  MacDoanld, Nicola D.⁴  Tucci, Arianna¹  Nanji, Tina^1,2  Pittman, Alan^1,3  de Silva, Rohan^1,3  Holton, Janice L.^1,3  Revesz, Tamas^1,3  Sweeney, Mary G.^1,2  Singleton, Andy B.⁵  Lees, Andrew J.^1,3  Bhatia, Kailash P.⁶  Houlden, Henry^1,2,4 

[1] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England

[2] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Neurogenet Lab, London WC1N 3BG, England

[3] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Queen Sq Brain Bank, Reta Lila Weston Inst Neurol Studies, London WC1N 3BG, England

[4] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England

[5] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[6] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Sobell Dept Movement Disorders, London WC1N 3BG, England

关键词: C9orf72;    Parkinsonism;    Multiple system atrophy (MSA);    Progressive supranuclear palsy (PSP);    Corticobasal degeneration (CBD) and corticobasal syndrome (CBS);   

DOI  :  10.1016/j.neurobiolaging.2014.08.024

来源: Elsevier

【 摘 要 】

A GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia. There is suggestion that these expansions may be a rare cause of parkinsonian disorders such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). Screening the C9orf72 gene in 37 patients with features of corticobasal syndrome (CBS) detected an expansion in 3 patients, confirmed by Southern blotting. In a series of 22 patients with clinically diagnosed PSP, we found 1 patient with an intermediate repeat length. We also screened for the C9orf72 expansion in a large series of neuro-pathologically confirmed samples with MSA (n = 96), PSP (n = 177), and CBD (n = 18). Patients were found with no more than 22 GGGGCC repeats. Although these results still need to be confirmed in a larger cohort of CBS and/or CBD patients, these data suggest that in the presence of a family history and/or motor neuron disease features, patients with CBS or clinical PSP should be screened for the C9orf72 repeat expansion. In addition, we confirm that the C9orf72 expansions are not associated with pathologically confirmed MSA, PSP, or CBD in a large series of cases. (C) 2015 The Authors. Published by Elsevier Inc. All rights reserved.

【 授权许可】

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