C9orf72 expansions in frontotemporal dementia and amyotrophic lateral sclerosis

被引：196

作者：

Rohrer, Jonathan D. ^{[1
]}

Isaacs, Adrian M. ^{[2
]}

Mizlienska, Sarah ^{[2
]}

Mead, Simon ^{[3
]}

Lashley, Tammaryn ^{[4
]}

Wray, Selina ^{[5
]}

Sidle, Katie ^{[5
]}

Fratta, Pietro ^{[2
]}

Orrell, Richard W. ^{[5
]}

Hardy, John ^{[5
]}

Holton, Janice ^{[4
]}

Revesz, Tamas ^{[4
]}

Rossor, Martin N. ^{[1
]}

Warren, Jason D. ^{[1
]}

机构：

[1] UCL, Dementia Res Ctr, Inst Neurol, London, England

[2] UCL, Inst Neurol, Dept Neurodegenerat Dis, London, England

[3] UCL, Inst Neurol, MRC, Prion Unit, London, England

[4] UCL, Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England

[5] UCL, Inst Neurol, Dept Mol Neurosci, London, England

来源：

LANCET NEUROLOGY | 2015年 / 14卷 / 03期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HEXANUCLEOTIDE REPEAT EXPANSION; G-QUADRUPLEX STRUCTURES; GGGGCC-REPEAT; RNA FOCI; BEHAVIORAL VARIANT; LOBAR DEGENERATION; CLINICAL CHARACTERISTICS; PATHOLOGICAL FEATURES; ANTISENSE TRANSCRIPTS; BIPOLAR DISORDER;

D O I：

10.1016/S1474-4422(14)70233-9

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

C9orf72 hexanucleotide repeat expansions are the most common cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. The clinical presentation is often indistinguishable from classic FTD or ALS, although neuropsychiatric symptoms are more prevalent and, for ALS, behavioural and cognitive symptoms occur more frequently. Pathogenic repeat length is in the hundreds or thousands, but the minimum length that increases risk of disease, and how or whether the repeat size affects phenotype, are unclear. Like in many patients with FTD and ALS, neuronal inclusions that contain TARDBP are seen, but are not universal, and the characteristic pathological finding is of dipeptide repeat (DPR) proteins, formed by unconventional repeat-associated non-ATG translation. Possible mechanisms of neurodegeneration include loss of C9orf72 protein and function, RNA toxicity, and toxicity from the DPR proteins, but which of these is the major pathogenic mechanism is not yet certain.

引用

页码：291 / 301

页数：11

共 140 条

[1] The GGGGCC Repeat Expansion in C9ORF72 in a Case with Discordant Clinical and FDG-PET Findings: PET Trumps Syndrome [J].

Adeli, Anahita ;

Savica, Rodolfo ;

Lowe, Val J. ;

Vemuri, Prashanthi ;

Knopman, David S. ;

DeJesus-Hernandez, Mariely ;

Rademakers, Rosa ;

Fields, Julie A. ;

Crum, Brian A. ;

Jack, Clifford R. ;

Petersen, Ronald C. ;

Boeve, Bradley F. .

NEUROCASE, 2014, 20 (01) :110-120

[2] A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories [J].

Akimoto, Chizuru ;

Volk, Alexander E. ;

van Blitterswijk, Marka ;

Van den Broeck, Marleen ;

Leblond, Claire S. ;

Lumbroso, Serge ;

Camu, William ;

Neitzel, Birgit ;

Onodera, Osamu ;

van Rheenen, Wouter ;

Pinto, Susana ;

Weber, Markus ;

Smith, Bradley ;

Proven, Melanie ;

Talbot, Kevin ;

Keagle, Pamela ;

Chesi, Alessandra ;

Ratti, Antonia ;

van der Zee, Julie ;

Alstermark, Helena ;

Birve, Anna ;

Calini, Daniela ;

Nordin, Angelica ;

Tradowsky, Daniela C. ;

Just, Walter ;

Daoud, Hussein ;

Angerbauer, Sabrina ;

DeJesus-Hernandez, Mariely ;

Konno, Takuya ;

Lloyd-Jani, Anjali ;

de Carvalho, Mamede ;

Mouzat, Kevin ;

Landers, John E. ;

Veldink, Jan H. ;

Silani, Vincenzo ;

Gitler, Aaron D. ;

Shaw, Christopher E. ;

Rouleau, Guy A. ;

van den Berg, Leonard H. ;

Van Broeckhoven, Christine ;

Rademakers, Rosa ;

Andersen, Peter M. ;

Kubisch, Christian .

JOURNAL OF MEDICAL GENETICS, 2014, 51 (06) :419-424

[3] p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS [J].

Al-Sarraj, Safa ;

King, Andrew ;

Troakes, Claire ;

Smith, Bradley ;

Maekawa, Satomi ;

Bodi, Istvan ;

Rogelj, Boris ;

Al-Chalabi, Ammar ;

Hortobagyi, Tibor ;

Shaw, Christopher E. .

ACTA NEUROPATHOLOGICA, 2011, 122 (06) :691-702

[4] Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons [J].

Almeida, Sandra ;

Gascon, Eduardo ;

Tran, Helene ;

Chou, Hsin Jung ;

Gendron, Tania F. ;

DeGroot, Steven ;

Tapper, Andrew R. ;

Sellier, Chantal ;

Charlet-Berguerand, Nicolas ;

Karydas, Anna ;

Seeley, William W. ;

Boxer, Adam L. ;

Petrucelli, Leonard ;

Miller, Bruce L. ;

Gao, Fen-Biao .

ACTA NEUROPATHOLOGICA, 2013, 126 (03) :385-399

[5]

[Anonymous], NEUROBIOL AGING

[6] Early Onset Behavioral Variant Frontotemporal Dementia due to the C9ORF72 Hexanucleotide Repeat Expansion: Psychiatric Clinical Presentations [J].

Arighi, Andrea ;

Fumagalli, Giorgio G. ;

Jacini, Francesca ;

Fenoglio, Chiara ;

Ghezzi, Laura ;

Pietroboni, Anna M. ;

De Riz, Milena ;

Serpente, Maria ;

Ridolfi, Elisa ;

Bonsi, Rossana ;

Bresolin, Nereo ;

Scarpini, Elio ;

Galimberti, Daniela .

JOURNAL OF ALZHEIMERS DISEASE, 2012, 31 (02) :447-452

[7] Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS [J].

Ash, Peter E. A. ;

Bieniek, Kevin F. ;

Gendron, Tania F. ;

Caulfield, Thomas ;

Lin, Wen-Lang ;

DeJesus-Hernandez, Mariely ;

van Blitterswijk, Marka M. ;

Jansen-West, Karen ;

Paul, Joseph W., III ;

Rademakers, Rosa ;

Boylan, Kevin B. ;

Dickson, Dennis W. ;

Petrucelli, Leonard .

NEURON, 2013, 77 (04) :639-646

[8] Large C9orf72 Hexanucleotide Repeat Expansions Are Seen in Multiple Neurodegenerative Syndromes and Are More Frequent Than Expected in the UK Population [J].

Beck, Jon ;

Poulter, Mark ;

Hensman, Davina ;

Rohrer, Jonathan D. ;

Mahoney, Colin J. ;

Adamson, Gary ;

Campbell, Tracy ;

Uphill, James ;

Borg, Aaron ;

Fratta, Pietro ;

Orrell, Richard W. ;

Malaspina, Andrea ;

Rowe, James ;

Brown, Jeremy ;

Hodges, John ;

Sidle, Katie ;

Polke, James M. ;

Houlden, Henry ;

Schott, Jonathan M. ;

Fox, Nick C. ;

Rossor, Martin N. ;

Tabrizi, Sarah J. ;

Isaacs, Adrian M. ;

Hardy, John ;

Warren, Jason D. ;

Collinge, John ;

Mead, Simon .

AMERICAN JOURNAL OF HUMAN GENETICS, 2013, 92 (03) :345-353

[9] Basal ganglia involvement in amyotrophic lateral sclerosis [J].

Bede, Peter ;

Elamin, Marwa ;

Byrne, Susan ;

McLaughlin, Russell L. ;

Kenna, Kevin ;

Vajda, Alice ;

Pender, Niall ;

Bradley, Daniel G. ;

Hardiman, Orla .

NEUROLOGY, 2013, 81 (24) :2107-2115

[10] Multiparametric MRI study of ALS stratified for the C9orf72 genotype [J].

Bede, Peter ;

Bokde, Arun L. W. ;

Byrne, Susan ;

Elamin, Marwa ;

McLaughlin, Russell L. ;

Kenna, Kevin ;

Fagan, Andrew J. ;

Pender, Niall ;

Bradley, Daniel G. ;

Hardiman, Orla .

NEUROLOGY, 2013, 81 (04) :361-369

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