Abstract
The hexanucleotide repeat expansions in the C9ORF72 gene has been found in some patients with atypical Parkinsonism. A number of hexanucleotide repeats were examined in a Chinese population, including 619 patients with Parkinson’s disease (PD), 381 patients with multiple system atrophy (MSA), and 632 healthy controls. We did not identify any pathogenic repeat expansions in either patients or controls, and any associations between repeats number and disease risk. C9ORF72 expansions are not involved the wider spectrum of Parkinsonism.
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References
Akimoto C, Forsgren L, Linder J, Birve A, Backlund I, Andersson J, Nilsson AC, Alstermark H, Andersen PM (2013) No GGGGCC-hexanucleotide repeat expansion in C9ORF72 in parkinsonism patients in Sweden. Amyotroph Lateral Scler Frontotemporal Degener 14(1):26–29. doi:10.3109/17482968.2012.725415
Beck J, Poulter M, Hensman D, Rohrer JD, Mahoney CJ, Adamson G, Campbell T, Uphill J, Borg A, Fratta P, Orrell RW, Malaspina A, Rowe J, Brown J, Hodges J, Sidle K, Polke JM, Houlden H, Schott JM, Fox NC, Rossor MN, Tabrizi SJ, Isaacs AM, Hardy J, Warren JD, Collinge J, Mead S (2013) Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population. Am J Hum Genet 92(3):345–353. doi:10.1016/j.ajhg.2013.01.011
Chen Y, Lin Z, Chen X, Cao B, Wei Q, Ou R, Zhao B, Song W, Wu Y, Shang HF (2016) Large C9orf72 repeat expansions are seen in Chinese patients with sporadic amyotrophic lateral sclerosis. Neurobiol Aging 38(217):e215–e222. doi:10.1016/j.neurobiolaging.2015.11.016
Cooper-Knock J, Frolov A, Highley JR, Charlesworth G, Kirby J, Milano A, Hartley J, Ince PG, McDermott CJ, Lashley T, Revesz T, Shaw PJ, Wood NW, Bandmann O (2013) C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic study. Neurology 81(9):808–811. doi:10.1212/WNL.0b013e3182a2cc38
Cruts M, Gijselinck I, Van Langenhove T, van der Zee J, Van Broeckhoven C (2013) Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum. Trends Neurosci 36(8):450–459. doi:10.1016/j.tins.2013.04.010
Daoud H, Noreau A, Rochefort D, Paquin-Lanthier G, Gauthier MT, Provencher P, Pourcher E, Dupre N, Chouinard S, Jodoin N, Soland V, Fon EA, Dion PA, Dion PA, Rouleau GA (2013) Investigation of C9orf72 repeat expansions in Parkinson’s disease. Neurobiol Aging 34(6):1710. doi:10.1016/j.neurobiolaging.2012.11.025 (e1717–1719)
Dejesus-Hernandez M, Rayaprolu S, Soto-Ortolaza AI, Rutherford NJ, Heckman MG, Traynor S, Strongosky A, Graff-Radford N, Van Gerpen J, Uitti RJ, Shih JJ, Lin SC, Wszolek ZK, Rademakers R, Ross OA (2013) Analysis of the C9orf72 repeat in Parkinson’s disease, essential tremor and restless legs syndrome. Parkinsonism Relat Disord 19(2):198–201. doi:10.1016/j.parkreldis.2012.09.013
Goldman JS, Quinzii C, Dunning-Broadbent J, Waters C, Mitsumoto H, Brannagan TH 3rd, Cosentino S, Huey ED, Nagy P, Kuo SH (2014) Multiple system atrophy and amyotrophic lateral sclerosis in a family with hexanucleotide repeat expansions in C9orf72. JAMA Neurol 71(6):771–774. doi:10.1001/jamaneurol.2013.5762
Harms MB, Neumann D, Benitez BA, Cooper B, Carrell D, Racette BA, Perlmutter JS, Goate A, Cruchaga C (2013) Parkinson disease is not associated with C9ORF72 repeat expansions. Neurobiol Aging 34(5):1519. doi:10.1016/j.neurobiolaging.2012.10.001 (e1511–1512)
Hsiung GY, DeJesus-Hernandez M, Feldman HH, Sengdy P, Bouchard-Kerr P, Dwosh E, Butler R, Leung B, Fok A, Rutherford NJ, Baker M, Rademakers R, Mackenzie IR (2012) Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain 135(Pt 3):709–722. doi:10.1093/brain/awr354
Hubers A, Marroquin N, Schmoll B, Vielhaber S, Just M, Mayer B, Hogel J, Dorst J, Mertens T, Just W, Aulitzky A, Wais V, Ludolph AC, Kubisch C, Weishaupt JH, Volk AE (2014) Polymerase chain reaction and Southern blot-based analysis of the C9orf72 hexanucleotide repeat in different motor neuron diseases. Neurobiol Aging 35(5):1214. doi:10.1016/j.neurobiolaging.2013.11.034 (e1211–1216)
Jiao B, Guo JF, Wang YQ, Yan XX, Zhou L, Liu XY, Zhang FF, Zhou YF, Xia K, Tang BS, Shen L (2013) C9orf72 mutation is rare in Alzheimer’s disease, Parkinson’s disease, and essential tremor in China. Front Cell Neurosci 7:164. doi:10.3389/fncel.2013.00164
Lesage S, Le Ber I, Condroyer C, Broussolle E, Gabelle A, Thobois S, Pasquier F, Mondon K, Dion PA, Rochefort D, Rouleau GA, Durr A, Brice A (2013) C9orf72 repeat expansions are a rare genetic cause of parkinsonism. Brain 136(Pt 2):385–391. doi:10.1093/brain/aws357
Lin CH, Chen TF, Chiu MJ, Lin HI, Wu RM (2014) Lack of c9orf72 repeat expansion in taiwanese patients with mixed neurodegenerative disorders. Front Neurol 5:59. doi:10.3389/fneur.2014.00059
Lindquist SG, Duno M, Batbayli M, Puschmann A, Braendgaard H, Mardosiene S, Svenstrup K, Pinborg LH, Vestergaard K, Hjermind LE, Stokholm J, Andersen BB, Johannsen P, Nielsen JE (2013) Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease. Clin Genet 83(3):279–283. doi:10.1111/j.1399-0004.2012.01903.x
Luigetti M, Quaranta D, Conte A, Piccininni C, Lattante S, Romano A, Silvestri G, Zollino M, Sabatelli M (2013) Frontotemporal dementia, Parkinsonism and lower motor neuron involvement in a patient with C9ORF72 expansion. Amyotroph Lateral Scler Frontotemporal Degener 14(1):66–69. doi:10.3109/17482968.2012.692383
Majounie E, Abramzon Y, Renton AE, Keller MF, Traynor BJ, Singleton AB (2012a) Large C9orf72 repeat expansions are not a common cause of Parkinson’s disease. Neurobiol Aging 33(10):2527. doi:10.1016/j.neurobiolaging.2012.05.007 (e2521–2522)
Majounie E, Renton AE, Mok K, Dopper EG, Waite A, Rollinson S, Chio A, Restagno G, Nicolaou N, Simon-Sanchez J, van Swieten JC, Abramzon Y, Johnson JO, Sendtner M, Pamphlett R, Orrell RW, Mead S, Sidle KC, Houlden H, Rohrer JD, Morrison KE, Pall H, Talbot K, Ansorge O, Hernandez DG, Arepalli S, Sabatelli M, Mora G, Corbo M, Giannini F, Calvo A, Englund E, Borghero G, Floris GL, Remes AM, Laaksovirta H, McCluskey L, Trojanowski JQ, Van Deerlin VM, Schellenberg GD, Nalls MA, Drory VE, Lu CS, Yeh TH, Ishiura H, Takahashi Y, Tsuji S, Le Ber I, Brice A, Drepper C, Williams N, Kirby J, Shaw P, Hardy J, Tienari PJ, Heutink P, Morris HR, Pickering-Brown S, Traynor BJ (2012b) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 11(4):323–330. doi:10.1016/S1474-4422(12)70043-1
Nuytemans K, Bademci G, Kohli MM, Beecham GW, Wang L, Young JI, Nahab F, Martin ER, Gilbert JR, Benatar M, Haines JL, Scott WK, Zuchner S, Pericak-Vance MA, Vance JM (2013) C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease. Ann Hum Genet 77(5):351–363. doi:10.1111/ahg.12033
Nuytemans K, Inchausti V, Beecham GW, Wang L, Dickson DW, Trojanowski JQ, Lee VM, Mash DC, Frosch MP, Foroud TM, Honig LS, Montine TJ, Dawson TM, Martin ER, Scott WK, Vance JM (2014) Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson’s disease. Mov Disord 29(6):827–830. doi:10.1002/mds.25838
Savica R, Adeli A, Vemuri P, Knopman DS, Dejesus-Hernandez M, Rademakers R, Fields JA, Whitwell J, Jack CR, Lowe V, Petersen RC, Boeve BF (2012) Characterization of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72. Arch Neurol 69(9):1164–1169. doi:10.1001/archneurol.2012.772
Scholz SW, Majounie E, Revesz T, Holton JL, Okun MS, Houlden H, Singleton AB (2015) Multiple system atrophy is not caused by C9orf72 hexanucleotide repeat expansions. Neurobiol Aging 36(2):1223. doi:10.1016/j.neurobiolaging.2014.08.033 (e1221–1222)
Schottlaender LV, Polke JM, Ling H, MacDoanld ND, Tucci A, Nanji T, Pittman A, de Silva R, Holton JL, Revesz T, Sweeney MG, Singleton AB, Lees AJ, Bhatia KP, Houlden H (2014) The analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2014.08.024
Smith BN, Newhouse S, Shatunov A, Vance C, Topp S, Johnson L, Miller J, Lee Y, Troakes C, Scott KM, Jones A, Gray I, Wright J, Hortobagyi T, Al-Sarraj S, Rogelj B, Powell J, Lupton M, Lovestone S, Sapp PC, Weber M, Nestor PJ, Schelhaas HJ, Asbroek AA, Silani V, Gellera C, Taroni F, Ticozzi N, Van den Berg L, Veldink J, Van Damme P, Robberecht W, Shaw PJ, Kirby J, Pall H, Morrison KE, Morris A, de Belleroche J, Vianney de Jong JM, Baas F, Andersen PM, Landers J, Brown RH Jr, Weale ME, Al-Chalabi A, Shaw CE (2013) The C9ORF72 expansion mutation is a common cause of ALS ± FTD in Europe and has a single founder. Eur J Hum Genet 21(1):102–108. doi:10.1038/ejhg.2012.98
Takada LT, Pimentel ML, Dejesus-Hernandez M, Fong JC, Yokoyama JS, Karydas A, Thibodeau MP, Rutherford NJ, Baker MC, Lomen-Hoerth C, Rademakers R, Miller BL (2012) Frontotemporal dementia in a Brazilian kindred with the c9orf72 mutation. Arch Neurol 69(9):1149–1153. doi:10.1001/archneurol.2012.650
Theuns J, Verstraeten A, Sleegers K, Wauters E, Gijselinck I, Smolders S, Crosiers D, Corsmit E, Elinck E, Sharma M, Kruger R, Lesage S, Brice A, Chung SJ, Kim MJ, Kim YJ, Ross OA, Wszolek ZK, Rogaeva E, Xi Z, Lang AE, Klein C, Weissbach A, Mellick GD, Silburn PA, Hadjigeorgiou GM, Dardiotis E, Hattori N, Ogaki K, Tan EK, Zhao Y, Aasly J, Valente EM, Petrucci S, Annesi G, Quattrone A, Ferrarese C, Brighina L, Deutschlander A, Puschmann A, Nilsson C, Garraux G, LeDoux MS, Pfeiffer RF, Boczarska-Jedynak M, Opala G, Maraganore DM, Engelborghs S, De Deyn PP, Cras P, Cruts M, Van Broeckhoven C (2014) Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease. Neurology 83(21):1906–1913. doi:10.1212/WNL.0000000000001012
Ticozzi N, Tiloca C, Calini D, Gagliardi S, Altieri A, Colombrita C, Cereda C, Ratti A, Pezzoli G, Borroni B, Goldwurm S, Padovani A, Silani V (2014) C9orf72 repeat expansions are restricted to the ALS-FTD spectrum. Neurobiol Aging 35(4):936. doi:10.1016/j.neurobiolaging.2013.09.037 (e913–937)
Van Langenhove T, van der Zee J, Gijselinck I, Engelborghs S, Vandenberghe R, Vandenbulcke M, De Bleecker J, Sieben A, Versijpt J, Ivanoiu A, Deryck O, Willems C, Dillen L, Philtjens S, Maes G, Baumer V, Van Den Broeck M, Mattheijssens M, Peeters K, Martin JJ, Michotte A, Santens P, De Jonghe P, Cras P, De Deyn PP, Cruts M, Van Broeckhoven C (2013) Distinct clinical characteristics of C9orf72 expansion carriers compared with GRN, MAPT, and nonmutation carriers in a Flanders-Belgian FTLD cohort. JAMA Neurol 70(3):365–373. doi:10.1001/2013.jamaneurol.181
Xi Z, Zinman L, Grinberg Y, Moreno D, Sato C, Bilbao JM, Ghani M, Hernandez I, Ruiz A, Boada M, Moron FJ, Lang AE, Marras C, Bruni A, Colao R, Maletta RG, Puccio G, Rainero I, Pinessi L, Galimberti D, Morrison KE, Moorby C, Stockton JD, Masellis M, Black SE, Hazrati LN, Liang Y, van Haersma de With J, Fornazzari L, Villagra R, Rojas-Garcia R, Clarimon J, Mayeux R, Robertson J, St George-Hyslop P, Rogaeva E (2012) Investigation of c9orf72 in 4 neurodegenerative disorders. Arch Neurol 69(12):1583–1590. doi:10.1001/archneurol.2012.2016
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X. Chen and Y. Chen contributed equally to this work.
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Chen, X., Chen, Y., Wei, Q. et al. C9ORF72 repeat expansions in Chinese patients with Parkinson’s disease and multiple system atrophy. J Neural Transm 123, 1341–1345 (2016). https://doi.org/10.1007/s00702-016-1598-2
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DOI: https://doi.org/10.1007/s00702-016-1598-2