Genetika 2022 Volume 54, Issue 3, Pages: 1313-1330
https://doi.org/10.2298/GENSR2203313M
Full text (
487 KB)
C9ORF72 repeat expansion is not associated with atypical parkinsonism in the Serbian population
Marjanović Ana 
(Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia), ana.marjanovic@yahoo.com
Dobričić Valerija (Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia + Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany)
Ječmenica-Lukić Milica (Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
Stanković Iva (Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
Milićević Ognjen (Faculty of Medicine, University of Belgrade, Belgrade, Serbia)
Dragašević-Mišković Nataša (Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
Branković Marija (Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
Janković Milena (Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
Novaković Ivana (Faculty of Medicine, University of Belgrade, Belgrade, Serbia)
Svetel Marina (Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
Stefanova Elka (Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
Kostić Vladimir (Faculty of Medicine, University of Belgrade, Belgrade, Serbia + Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia)
These include, among others, two forms of atypical Parkinsonism, multiple
system atrophy (MSA) and progressive supranuclear palsy (PSP). This study
aimed to assess the potential role of C9orf72 repeat expansions among
Serbian patients diagnosed with MSA and PSP. Genomic DNA of 44 MSA patients,
73 PSP patients, and 96 controls was extracted from peripheral blood, and
normal C9orf72 alleles were analyzed by standard quantitative fluorescence
polymerase chain reaction (QF-PCR) and fragment analysis. Subsequently, for
all samples presenting a single allele, repeat-primed PCR was performed with
two different sets of primers to avoid a false-negative result. Thirty
repeats were used as a pathogenic cut-off and 20-29 repeats for the
intermediate alleles. No pathological C9orf72 expansions were detected in
the MSA and PSP patients nor the control subjects. In the MSA group, the
most common was the allele with 2 repeats, and the largest repeat number was
14. Among PSP patients, the most common allele also had 2 repeats, while the
largest detected repeat size within the normal range was 17. Also, we
identified one PSP patient that had an intermediate size allele (25
repeats). We did not find correlation between the number of repeats and
disease onset, age at the time of examination, or disease duration in MSA or
PSP patients. Regarding family history, in PSP the sum of both allele
repeats numbers was higher in patients with positive family history than in
sporadic cases. The results presented in this study are the first systematic
assessment of C9orf72 allele sizes among patients diagnosed with MSA and PSP
in the Serbian population. Although the potential role of intermediate
C9orf72 repeats in neurodegenerative disorders is still to be elucidated,
our results support the current knowledge that C9orf72 repeat expansions are
not associated with MSA and PSP.
Keywords: atypical Parkinsonism, C9orf72, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), repeat expansion
Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. ON175090, Grant no. ON175091, Grant no. 200110
Show references
AKIMOTO, C.,L., J., FORSGREN, A., LINDER, I., BIRVE, J., BACKLUND, A.C., ANDERSSON, H., NILSSON, P.M., ALSTERMARK, ANDERSEN (2013): No GGGGCC-hexanucleotiderepeat expansion in C9ORF72 in parkinsonism patients in Sweden. Amyotroph Lateral Scler Frontotemporal degener., 14(1): 26-29.
BAKER, M., I., LITVAN, H., HOULDEN, J., ADAMSON, D., DICKSON, J., PEREZ-TUR, J.HARDY, T., LYNCH, E., BIGIO, M., HUTTON (1999): Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum. Mol. Genet., 8(4), 711-715.
BECK, J., M., POULTER, D., HENSMAN, J.D., ROHRER, C.J., MAHONEY, G., ADAMSON, T., CAMPBELL, J., UPHILL, A., BORG, P., FRATTA, R.W., ORRELL, A., MALASPINA, J., ROWE, J., BROWN, J., HODGES, K., SIDLE, J.M., POLKE, H., HOULDEN, J.M., SCHOTT, N.C., FOX, M.N., ROSSOR, S.J., TABRIZI, A.M., ISAACS, J., HARDY, J.D., WARREN, J., COLLINGE, S., MEAD (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.
BOEVE, B.F., K.B., BOYLAN, N.R., GRAFF-RADFORD, M., DEJESUS-HERNANDEZ, D.S., KNOPMAN, O., PEDRAZA, P., VEMURI, D., JONES, V., LOWE, M.E., MURRAY, D.W., DICKSON, K.A., JOSEPHS, B.K., RUSH, M.M., MACHULDA, J.A., FIELDS, T.J., FERMAN, M., BAKER, N.J., RUTHERFORD, J., ADAMSON, Z.K., WSZOLEK, A., ADELI, R., SAVICA, B., BOOT, K.M., KUNTZ, R., GAVRILOVA, A., REEVES, J., WHITWELL, K., KANTARCI, C.R., JACK JR, J.E., PARISI, J.A., LUCAS, R.C., PETERSEN, R., RADEMAKERS (2012): Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain, 135(Pt 3):765-783.
BOURINARIS, T., H., HOULDEN (2018): C9orf72 and its Relevance in Parkinsonism and Movement Disorders: A Comprehensive Review of the Literature. Mov. Disord. Clin. Pract., 5(6):575-585.
BROOKS, J.A., H., HOULDEN, A., MELCHERS, A.J., ISLAM, J., DING, A., LI, R., PAUDEL, T., REVESZ, J.L., HOLTON, N., WOOD, A., LEES, A.B., SINGLETON, S.W., SCHOLZ (2011): Mutational analysis of parkin and PINK1 in multiple system atrophy. Neurobiol Aging., 32(3): 548.e5-e7.
BYRNE, S., M., HEVERIN, M., ELAMIN, C., WALSH, O., HARDIMAN, (2014): Intermediate repeat expansion length in C9orf72 may be pathological in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener., 15(1-2):148-150.
CACACE, R., C., VAN CAUWENBERGHE, K., BETTENS, I., GIJSELINCK, J., VAN DER, ZEE, S., ENGELBORGHS, M., VANDENBULCKE, J., VAN DONGEN, V., BÄUMER, L., DILLEN, M., MATTHEIJSSENS, K., PEETERS, M., CRUTS, R., VANDENBERGHE, P.P., DEDEYN, C., VAN BROECKHOVEN, K., SLEEGERS (2013): C9orf72 G4C2 repeat expansions in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging., 34(6): 1712.e1-e7.
CALI, C.P., M., PATINO, Y.K., TAI, W.Y., HO, C.A., MCLEAN, C.M., MORRIS, W.W., SEELEY, B.L., MILLER, C., GAIG, J.P.G., VONSATTEL, C.L., WHITE 3RD, S., ROEBER, H., KRETZSCHMAR, J.C., TRONCOSO, C., TROAKES, M., GEARING, B., GHETTI, V.M., VAN DEERLIN, V.M., LEE, J.Q., TROJANOWSKI, K.Y., MOK, H., LING, D.W., DICKSON, G.D., SCHELLENBERG, S.C., LING, E.B., LEE (2019): C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy. Acta Neuropathol., 138(5):795-811.
CANNAS, A., P., SOLLA, G., BORGHERO, G.L., FLORIS, A., CHIO, M.M., MASCIA, N., MODUGNO, A., MURONI, G., OROFINO, F., DI STEFANO, A., CALVO, C., MOGLIA, G., RESTAGNO, M., MELONI, R., FARRIS, D., CIACCIO, R., PUDDU, M.I., VACCA, R., MELIS, M.R., MURRU, S., TRANQUILLI, D., CORONGIU, M., ROLESU, S., CUCCU, M.G., MARROSU, F., MARROSU (2015): C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson’s disease complicated by psychosis or dementia in a Sardinian population. J Neurol., 262(11):2498-2503.
CHEN, X., Y., CHEN, Q., WEI, R., OU, B., CAO, B., ZHAO, H.F., SHANG (2016): C9ORF72 repeat expansions in Chinese patients with Parkinson’s disease and multiple system atrophy. J.Neural. Transm (Vienna), 123(11):1341-1345.
CHEN, Z., J.A., CHEN, A., SHATUNOV, A.R., JONES, S.N., KRAVITZ, A.Y., HUANG, L., LAWRENCE, J.K., LOWE, C.M., LEWIS, C.A.M., PAYAN, W., LIEB, A., FRANKE, P., DELOUKAS, P., AMOUYEL, C., TZOURIO, J.F., DARTIGUES, NNIPPS, BBBIPPS STUDY GROUPS, A., LUDOLPH, G., BENSIMON, P.N., LEIGH, J.M., BRONSTEIN, G., COPPOLA, D.H., GESCHWIND, A., AL-CHALABI (2019): Genome-wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy. Mov Disord., 34(7):1049-1059.
CHO, J.W., S.Y., KIM, S.S., PARK, B.S., JEON (2009): The G2019S LRRK2 Mutation is Rare in Korean Patients with Parkinson’s Disease and Multiple System Atrophy. J. Clin. Neurol., 5(1):29-32.
CONRAD, C., A., ANDREADIS, J.Q., TROJANOWSKI, D.W., DICKSON, D., KANG, X., CHEN, W., WIEDERHOLT, L., HANSEN, E., MASLIAH, L.J., THAL, R., KATZMAN, Y., XIA, T., SAITOH (1997): Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol., 41(2):277-281.
DEJESUS-HERNANDEZ, M., I.R., MACKENZIE, B.F., BOEVE, A.L., BOXER, M., BAKER, N.J., RUTHERFORD, A.M., NICHOLSON, N.A., FINCH, H., FLYNN, J., ADAMSON, N., KOURI, A., WOJTAS, P., SENGDY, G.Y., HSIUNG, A., KARYDAS, W.W., SEELEY, K.A., JOSEPHS, G., COPPOLA, D.H., GESCHWIND, Z.K., WSZOLEK, H., FELDMAN, D.S., KNOPMAN, R.C., PETERSEN, B.L., MILLER, D.W., DICKSON, K.B., BOYLAN, N.R., GRAFF-RADFORD, R., RADEMAKERS (2011): Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron., 72(2):245-256.
DEJESUS-HERNANDEZ, M., S., RAYAPROLU, A.I., SOTO-ORTOLAZA, N.J., RUTHERFORD, M.G., HECKMAN, S., TRAYNOR, A., STRONGOSKY, N., GRAFF-RADFORD, J., VAN GERPEN, R.J., UITTI, J.J., SHIH, S.C., LIN, Z.K., WSZOLEK, R., RADEMAKERS, O.A., ROSS (2013): Analysis of the C9orf72 repeat in Parkinson’s disease, essential tremor and restless legs syndrome. Parkinsonism Relat Disord., 19(2):198-201.
FEDEROFF, M., L.V., SCHOTTLAENDER, H., HOULDEN, A., SINGLETON (2015): Multiple system atrophy: the application of genetics in understanding etiology. Clin. Auton. Res., 25(1):19-36.
GAIG, C., M., EZQUERRA, M.J., MARTÍ, F., VALLDEORIOLA, E., MUÑOZ, A., LLADÓ, M.J., REY, A., CARDOZO, J.L., MOLINUEVO, E., TOLOSA (2008): Screening for the LRRK2 G2019S and codon-1441 mutations in a pathological series of parkinsonian syndromes and frontotemporal lobar degeneration. J. Neurol. Sci., 270(1-2):94-98.
GALIMBERTI, D., C., FENOGLIO, M., SERPENTE, C., VILLA, R., BONSI, A., ARIGHI, G.G., FUMAGALLI, R., DEL BO, A.C., BRUNI, M., ANFOSSI, A., CLODOMIRO, C., CUPIDI, B., NACMIAS, S., SORBI, I., PIACERI, S., BAGNOLI, V., BESSI, A., MARCONE, C., CERAMI, S.F., CAPPA, M., FILIPPI, F., AGOSTA, G., MAGNANI, G., COMI, M., FRANCESCHI, I., RAINERO, M.T., GIORDANA, E., RUBINO, P., FERRERO, E., ROGAEVA, Z., XI, A.,CONFALONI, P., PISCOPO, G., BRUNO, G., TALARICO, A., CAGNIN, F., CLERICI, B., DELLOSSO, G.P., COMI, A.C., ALTAMURA, C., MARIANI, E., SCARPINI (2013):Autosomal dominant frontotemporal lobar degeneration due to the C9ORF72 hexanucleotide repeat expansion: late-onset psychotic clinical presentation. Biol. Psychiatry, 74(5):384-391.
GIJSELINCK, I., S., VAN MOSSEVELDE, J., VAN DER ZEE, A., SIEBEN, S., ENGELBORGHS, J., DE BLEECKER, A., IVANOIU, O., DERYCK, D., EDBAUER, M., ZHANG, B., HEEMAN, V., BÄUMER, M., VAN DEN BROECK, M., MATTHEIJSSENS, K., PEETERS, E., ROGAEVA, P., DE JONGHE, P., CRAS, J.J., MARTIN, P.P., DE DEYN, M., CRUTS, C., VAN BROECKHOVEN (2016): The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter. Mol. Psychiatry, 21(8):1112-1124.
GILMAN, S., G.K., WENNING, P.A., LOW, D.J., BROOKS, C.J., MATHIAS, J.Q., TROJANOWSKI, N.W., WOOD, C., COLOSIMO, A., DÜRR, C.J., FOWLER, H., KAUFMANN, T., KLOCKGETHER, A., LEES, W., POEWE, N., QUINN, T., REVESZ, D., ROBERTSON, P., SANDRONI, K., SEPPI, M., VIDAILHET (2008): Second consensus statement on the diagnosis of multiple system atrophy. Neurology, 71(9):670-676.
GILMAN, S., P., LOW, N., QUINN, A., ALBANESE, Y., BEN-SHLOMO, C., FOWLER, H., KAUFMANN, T., KLOCKGETHER, A., LANG, P., LANTOS, I., LITVAN, C., MATHIAS, E., OLIVER, D., ROBERTSON, I., SCHATZ, G., WENNING (1998): Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. Clin. Auton. Res., 8(6):359-362.
GOKER-ALPAN, O., B.I., GIASSON, M.J., EBLAN, J., NGUYEN, H.I., HURTIG, V.M., LEE, J.Q., TROJANOWSKI, E., SIDRANSKY (2006): Glucocerebrosidase mutations are an important risk factor for Lewy body disorders. Neurology, 67(5):908-910.
GOLDMAN, J.S., C., QUINZII, J., DUNNING-BROADBENT, C., WATERS, H., MITSUMOTO, T.H., BRANNAGAN 3RD, S., COSENTINO, E.D., HUEY, P., NAGY, S.H., KUO (2014): Multiple system atrophy and amyotrophic lateral sclerosis in a family with hexanucleotide repeat expansions in C9orf72. JAMA Neurol., 71(6):771-774.
GÓMEZ-TORTOSA, E., J., GALLEGO, R., GUERRERO-LÓPEZ, A., MARCOS, E., GIL-NECIGA, M.J., SAINZ, A., DÍAZ, E., FRANCO-MACÍAS, M.J., TRUJILLO-TIEBAS, C., AYUSO, J., PÉREZ-PÉREZ (2013): C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration. Neurology, 80(4):366-370.
HAUTBERGUE, G.M., J.D., CLEARY, S., GUO, L.P.W., RANUM (2021): Therapeutic strategies for C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia. Curr. Opin. Neurol., 34(5):748-755.
HÖGLINGER, G.U., N.M., MELHEM, D.W., DICKSON, P.M., SLEIMAN, L.S., WANG, L., KLEI, R., RADEMAKERS, R., DE SILVA, I., LITVAN, D.E., RILEY, J.C., VAN SWIETEN, P., HEUTINK, Z.K., WSZOLEK, R.J., UITTI, J., VANDROVCOVA, H.I., HURTIG, R.G., GROSS, W., MAETZLER, S., GOLDWURM, E., TOLOSA, B., BORRONI, P., PASTOR, PSP GENETICS STUDY GROUP, L.B., CANTWELL, M.R., HAN, A., DILLMAN, M.P., VAN DER BRUG, J.R., GIBBS, M.R., COOKSON, D.G., HERNANDEZ, A.B., SINGLETON, M.J., FARRER, C.E., YU, L.I., GOLBE, T., REVESZ, J., HARDY, A.J., LEES, B., DEVLIN, H., HAKONARSON, U., MÜLLER, G.D., SCHELLENBERG (2011): Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet., 43(7):699-705.
HÖGLINGER, G.U., G., RESPONDEK, M., STAMELOU, C., KURZ, K.A., JOSEPHS, A.E., LANG, B., MOLLENHAUER, U., MÜLLER, C., NILSSON, J.L., WHITWELL, T., ARZBERGER, E., ENGLUND, E., GELPI, A., GIESE, D.J., IRWIN, W.G., MEISSNER, A., PANTELYAT, A., RAJPUT, J.C., VAN SWIETEN, C., TROAKES, A., ANTONINI, K.P., BHATIA, Y., BORDELON, Y., COMPTA, J.C., CORVOL, C., COLOSIMO, D.W., DICKSON, R., DODEL, L., FERGUSON, M., GROSSMAN, J., KASSUBEK, F., KRISMER, J., LEVIN, S., LORENZL, H.R., MORRIS, P., NESTOR, W.H., OERTEL, W., POEWE, G., RABINOVICI, J.B., ROWE, G.D., SCHELLENBERG, K., SEPPI, T., VAN EIMEREN, G.K., WENNING, A.L., BOXER, L.I., GOLBE, I., LITVAN, MOVEMENT DISORDER SOCIETY-ENDORSED PSP STUDY GROUP (2017): Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord., 32(6):853-864.
HSIAO, C.T., P.C.,TSAI, Y.C., LIAO, Y.C., LEE, B.W., SOONG (2014): C9ORF72 repeat expansion is not a significant cause of late onset cerebellar ataxia syndrome. J. Neurol. Sci., 347(1-2):322-324.
IACOANGELI, A., A., AL KHLEIFAT, A.R., JONES, W., SPROVIERO, A., SHATUNOV, S., OPIE-MARTIN, ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE, K.E., MORRISON, P.J., SHAW, C.E., SHAW, I., FOGH, R.J., DOBSON, S.J., NEWHOUSE, A., AL-CHALABI (2019): C9orf72 intermediate expansions of 24-30 repeats are associated with ALS.Acta Neuropathol Commun., 7(1):115.
KOSTIĆ, V.S., V., DOBRIČIĆ, I., STANKOVIĆ, V., RALIĆ, E., STEFANOVA (2014): C9orf72expansion as a possible genetic cause of Huntington disease phenocopy syndrome. J Neurol., 261(10):1917-1921.
LE BER, I., A., CAMUZAT, L., GUILLOT-NOEL, D., HANNEQUIN, L., LACOMBLEZ, V., GOLFIER, M., PUEL, O., MARTINAUD, V., DERAMECOURT, S., RIVAUD-PECHOUX, S., MILLECAMPS, M., VERCELLETTO, P., COURATIER, F., SELLAL, F., PASQUIER, F., SALACHAS, C., THOMAS-ANTÉRION, M., DIDIC, J., PARIENTE, D., SEILHEAN, M., RUBERG, I., WARGON, F., BLANC, W., CAMU, B.F., MICHEL, E., BERGER, M., SAUVÉE, C.,THAUVIN-ROBINET, K., MONDON, E., TOURNIER-LASSERVE, C., GOIZET, M., FLEURY, G., VIENNET, P., VERPILLAT, V., MEININGER, C., DUYCKAERTS, B., DUBOIS, A., BRICE (2013): C9ORF72 repeat expansions in the frontotemporal dementias spectrum of diseases: a flow-chart for genetic testing. J Alzheimers Dis., 34(2):485-499.
LESAGE, S., I., LE BER, C., CONDROYER, E., BROUSSOLLE, A., GABELLE, S., THOBOIS, F., PASQUIER, K., MONDON, P.A., DION, D., ROCHEFORT, G.A., ROULEAU, A., DÜRR, A., BRICE, FRENCH PARKINSON’S DISEASE GENETICS STUDY GROUP (2013): C9orf72 repeat expansions are a rare genetic cause of parkinsonism. Brain., 136(Pt 2):385-391.
LINDQUIST, S.G., M., DUNO, M., BATBAYLI, A., PUSCHMANN, H., BRAENDGAARD, S., MARDOSIENE, K., SVENSTRUP, L.H., PINBORG, K., VESTERGAARD, L.E., HJERMIND, J., STOKHOLM, B.B., ANDERSEN, P., JOHANNSEN, J.E., NIELSEN (2013): Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease. Clin Genet., 83(3):279-283.
MAJOUNIE, E., A.E., RENTON, K., MOK, E.G., DOPPER, A., WAITE, S., ROLLINSON, A., CHIÒ, G., RESTAGNO, N., NICOLAOU, J., SIMON-SANCHEZ, J.C., VAN WIETEN, Y., ABRAMZON, J.O., JOHNSON, M., SENDTNER, R., PAMPHLETT, R.W., ORRELL, S., MEAD, K.C., SIDLE, H., HOULDEN, J.D., ROHRER, K.E., MORRISON, H., PALL, K., TALBOT, O., ANSORGE, CHROMOSOME 9-ALS/FTD CONSORTIUM; FRENCH RESEARCH NETWORK ON FTLD/FTLD/ALS; ITALSGEN CONSORTIUM, D.G., HERNANDEZ, S., AREPALLI, M. SABATELLI, G., MORA, M., CORBO, F., GIANNINI, A., CALVO, E., ENGLUND, G., BORGHERO, G.L., FLORIS, A.M., REMES, H., LAAKSOVIRTA, L., MCCLUSKEY, J.Q., TROJANOWSKI, V.M., VAN DEERLIN, G.D., SCHELLENBERG, M.A., NALLS, V.E., DRORY, C.S., LU, T.H., YEH, H., ISHIURA, Y., TAKAHASHI, S., TSUJI, I., LEBER, A., BRICE, C., DREPPER, N., WILLIAMS, J., KIRBY, P., SHAW, J., HARDY, P.J., TIENARI, P., HEUTINK, H.R., MORRIS, S., PICKERING-BROWN, B.J., TRAYNOR (2012): 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.
MAYL, K., C.E., SHAW, Y.B., LEE (2021): Disease Mechanisms and Therapeutic Approaches in C9orf72 ALS-FTD. Biomedicines., 9(6):601.
MCFARLAND, N.R. (2016): Diagnostic Approach to Atypical Parkinsonian Syndromes. Continuum (Minneap Minn)., 22(4 Movement Disorders):1117-1142.
MORRIS, H.R., J.R., VAUGHAN, S.R,. DATTA, R., BANDOPADHYAY, H.A., ROHAN DE SILVA, A., SCHRAG, N.J., CAIRNS, D., BURN, U., NATH, P.L., LANTOS, S., DANIEL, A.J., LEES, N.P., QUINN, N.W., WOOD (2000): Multiple system atrophy/progressive supranuclear palsy: alpha-Synuclein, synphilin, tau, and APOE. Neurology., 55(12):1918-1920.
MULTIPLE-SYSTEM ATROPHY RESEARCH COLLABORATION (2013): Mutations in COQ2 in familial and sporadic multiple-system atrophy. N. Engl. J. Med., 369(3):233-244.
NG, A.S.L., TAN EK (2017): Intermediate C9orf72 alleles in neurological disorders: does size really matter? J. Med. Genet., 54(9):591-597.
NICHOLL, D.J., P., BENNETT, L., HILLER, V., BONIFATI, N., VANACORE, G., FABBRINI, R., MARCONI, C., COLOSIMO, P., LAMBERTI, F., STOCCHI, U., BONUCCELLI, P., VIEREGGE, D.B., RAMSDEN, G., MECO, A.C., WILLIAMS (1999): A study of five candidate genes in Parkinson's disease and related neurodegenerative disorders. European Study Group on Atypical Parkinsonism. Neurology, 53(7):1415-1421.
NICHOLL, D.J., M.A., GREENSTONE, C.E., CLARKE, P., RIZZU, D., CROOKS, A., CROWE, J.Q., TROJANOWSKI, V.M., LEE, P., HEUTINK (2003): An English kindred with a novel recessive tauopathy and respiratory failure. Ann Neurol., 54(5):682-686.
NUYTEMANS, K., G., BADEMCI, M.M., KOHLI, G.W., BEECHAM, L., WANG, J.I., YOUNG, F., NAHAB, E.R., MARTIN, J.R., GILBERT, M., BENATAR, J.L., HAINES, W.K., SCOTT, S., ZÜCHNER, M.A., PERICAK-VANCE, J.M., VANCE (2013): C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease. Ann. Hum. Genet., 77(5):351-363.
NUYTEMANS, K., V., INCHAUSTI, G.W., BEECHAM, L., WANG, D.W., DICKSON, J.Q., TROJANOWSKI, V.M., LEE, D.C., MASH, M.P., FROSCH, T.M., FOROUD, L.S., HONIG, T.J., MONTINE, T.M., DAWSON, E.R., MARTIN, W.K., SCOTT, J.M., VANCE (2014): Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinsons disease. Mov. Disord., 29(6):827-830.
OGAKI, K., Y., LI, M., TAKANASHI, K., ISHIKAWA, T., KOBAYASHI, T., NONAKA, M., HASEGAWA, M., KISHI, H., YOSHINO, M., FUNAYAMA, T., TSUKAMOTO, K., SHIOYA, M., YOKOCHI, H., IMAI, R., SASAKI, Y., KOKUBO, S., KUZUHARA, Y., MOTOI, H., TOMIYAMA, N., HATTORI (2013): Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS. Parkinsonism Relat Disord., 19(1):15-20.
ORIGONE, P., S., VERDIANI, P., CIOTTI, R., GULLI, E., BELLONE, R., MARCHESE, G., ABBRUZZESE, P., MANDICH (2013): Enlarging the clinical spectrum associated with C9orf 72 repeat expansions: findings in an Italian cohort of patients with parkinsonian syndromes and relevance for genetic counselling. Amyotroph Lateral Scler. Frontotemporal Degener., 14(5-6):479-480.
POORKAJ, P., N.A., MUMA, V., ZHUKAREVA, E.J., COCHRAN, K.M., SHANNON, H., HURTIG, W.C., KOLLER, T.D., BIRD, J.Q., TROJANOWSKI, V.M., LEE, G.D., SCHELLENBERG (2002): An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann. Neurol., 52(4):511-516.
RENTON, A.E., E., MAJOUNIE, A., WAITE, J., SIMÓN-SÁNCHEZ, S., ROLLINSON, J.R., GIBBS, J.C., SCHYMICK, H., LAAKSOVIRTA, J.C., VAN SWIETEN, L., MYLLYKANGAS, H., KALIMO, A., PAETAU, Y., ABRAMZON, A.M., REMES, A., KAGANOVICH, S.W., SCHOLZ, J., DUCKWORTH, J., DING, D.W., HARMER, D.G., HERNANDEZ, J.O., JOHNSON, K., MOK, M., RYTEN, D., TRABZUNI, R.J., GUERREIRO, R.W., ORRELL, J., NEAL, A., MURRAY, J., PEARSON, I.E., JANSEN, D., SONDERVAN, H., SEELAAR, D., BLAKE, K.,YOUNG, N., HALLIWELL, J.B., CALLISTER, G., TOULSON, A., RICHARDSON, A., GERHARD, J., SNOWDEN, D., MANN, D., NEARY, M.A., NALLS, T., PEURALINNA, L., JANSSON, V.M., ISOVIITA, A.L., KAIVORINNE, M., HÖLTTÄ-VUORI, E., IKONEN, R., SULKAVA, M., BENATAR, J., WUU, A., CHIÒ, G., RESTAGNO, G., BORGHERO, M., SABATELLI, ITALSGEN CONSORTIUM, D., HECKERMAN, E., ROGAEVA, L., ZINMAN, J.D., ROTHSTEIN, M., SENDTNER, C. DREPPER, E.E., EICHLER, C., ALKAN, Z., ABDULLAEV, S.D., PACK, A., DUTRA, E., PAK, J., HARDY, A., SINGLETON, N.M., WILLIAMS, P., HEUTINK, S. PICKERING-BROWN, H.R., MORRIS, P.J., TIENARI, B.J.,TRAYNOR (2011): A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron., 72(2):257-268.
ROS, R., S., THOBOIS, N., STREICHENBERGER, N., KOPP, M.P., SÁNCHEZ, M., PÉREZ, J., HOENICKA, J., AVILA, J., HONNORAT, J.G., DE YÉBENES (2005): A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy. Arch Neurol., 62(9):1444-1450.
ROSS, O.A., A.J., WHITTLE, S.A., COBB, M.M., HULIHAN, S.J., LINCOLN, M., TOFT, M.J., FARRER, D.W., DICKSON (2006): Lrrk2 R1441 substitution and progressive supranuclear palsy. Neuropathol. Appl. Neurobiol., 32(1):23-25.
RUTHERFORD, N.J., M.G., HECKMAN, M., DEJESUS-HERNANDEZ, M.C., BAKER, A.I., SOTO-ORTOLAZA, S., RAYAPROLU, H., STEWART, E., FINGER, K., VOLKENING, W.W., SEELEY, K.J., HATANPAA, C., LOMEN-HOERTH, A., KERTESZ, E.H., BIGIO, C., LIPPA, D.S., KNOPMAN, H.A., KRETZSCHMAR, M., NEUMANN, R.J., CASELLI, C.L., WHITE 3RD, I.R., MACKENZIE, R.C., PETERSEN, M.J., STRONG, B.L., MILLER, B.F., BOEVE, R.J., UITTI, K.B., BOYLAN, Z.K., WSZOLEK, N.R., GRAFF-RADFORD, D.W., DICKSON, O.A., ROSS, R., RADEMAKERS (2012): Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype. Neurobiol. Aging., 33(12): 2950.e5-e7.
SAILER, A., S.W., SCHOLZ, M.A., NALLS, C., SCHULTE, M., FEDEROFF, T.R., PRICE, A., LEES, O.A., ROSS, D.W., DICKSON, K., MOK, N.E., MENCACCI, L., SCHOTTLAENDER, V., CHELBAN, H., LING, S.S., OSULLIVAN, N.W., WOOD, B.J., TRAYNOR, L., FERRUCCI, H.J., FEDEROFF, T.R., MHYRE, H.R., MORRIS, G., DEUSCHL, N., QUINN, H., WIDNER, A., ALBANESE, J., INFANTE, K.P., BHATIA, W., POEWE, W., OERTEL, G.U., HÖGLINGER, U., WÜLLNER, S., GOLDWURM, M.T., PELLECCHIA, J., FERREIRA, E., TOLOSA, B.R., BLOEM, O., RASCOL, W.G., MEISSNER, J.A., HARDY, T., REVESZ, J.L., HOLTON, T., GASSER, G.K., WENNING, A.B., SINGLETON, H., HOULDEN, EUROPEAN MULTIPLE SYSTEM ATROPHY STUDY GROUP AND THE UK MULTIPLE SYSTEM ATROPHY STUDY GROUP (2016): A genome-wide association study in multiple system atrophy. Neurology, 87(15):1591-1598.
SANCHEZ-CONTRERAS, M.Y., N., KOURI, C.N., COOK, D.J., SERIE, M.G., HECKMAN, N.A., FINCH, R.J., CASELLI, R.J., UITTI, Z.K., WSZOLEK, N., GRAFF-RADFORD, L., PETRUCELLI, L.S., WANG, G.D., SCHELLENBERG, D.W., DICKSON, R., RADEMAKERS, O.A., ROSS (2018): Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci. Mol. Neurodegener., 13(1):37.
SCHOLZ, S.W., H., HOULDEN, C., SCHULTE, M., SHARMA, A., LI, D., BERG, A., MELCHERS, R., PAUDEL, J.R., GIBBS, J., SIMON-SANCHEZ, C., PAISAN-RUIZ, J., BRAS, J., DING, H., CHEN, B.J., TRAYNOR, S., AREPALLI, R.R., ZONOZI, T., REVESZ, J., HOLTON, N., WOOD, A., LEES, W., OERTEL, U., WÜLLNER, S., GOLDWURM, M.T., PELLECCHIA, T., ILLIG, O., RIESS, H.H., FERNANDEZ, R.L., RODRIGUEZ, M.S., OKUN, W., POEWE, G.K., WENNING, J.A., HARDY, A.B., SINGLETON, F., DEL SORBO, S., SCHNEIDER, K.P., BHATIA, T., GASSER (2009): SNCA variants are associated with increased risk for multiple system atrophy. Ann. Neurol., 65(5):610-614.
SCHOLZ, S.W., E., MAJOUNIE, T., REVESZ, J.L., HOLTON, M.S., OKUN, H., HOULDEN, A.B., SINGLETON (2015): Multiple system atrophy is not caused by C9orf72 hexanucleotide repeat expansions. Neurobiol. Aging., 36(2): 1223.e1-e2.
SCHOTTLAENDER, L.V., J.M., POLKE, H., LING, N.D., MACDOANLD, A., TUCCI, T.,, NANJI, A., PITTMAN, R., DE SILVA, J.L., HOLTON, T., REVESZ, M.G., SWEENEY, A.B., SINGLETON, A.J., LEES, K.P., BHATIA, H., HOULDEN (2015): Analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism. Neurobiol. Aging., 36(2):1221.e1-e6.
SIMÓN-SÁNCHEZ, J., E.G., DOPPER, P.E., COHN-HOKKE, R.K., HUKEMA, N., NICOLAOU, H., SEELAAR, J.R., DE GRAAF, I., DE KONING, N.M., VAN SCHOOR, D.J., DEEG, M., SMITS, J., RAAPHORST, L.H., VAN DEN BERG, H.J., SCHELHAAS, C.E., DE DIE-SMULDERS, D., MAJOOR-KRAKAUER, A.J., ROZEMULLER, R., WILLEMSEN, Y.A., PIJNENBURG, P., HEUTINK, J.C., VAN SWIETEN (2012): The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions. Brain., 135(Pt 3):723-735.
SNOWDEN, J.S., S., ROLLINSON, C., LAFON, J., HARRIS, J., THOMPSON, A.M., RICHARDSON, M., JONES, A., GERHARD, D., NEARY, D.M., MANN, S., PICKERING- BROWN (2012): Psychosis, C9ORF72 and dementia with Lewy bodies. J. Neurol. Neurosurg. Psychiatry, 83(10):1031-1032.
SPANAKI, C., H., LATSOUDIS, A., PLAITAKIS (2006): LRRK2 mutations on Crete: R1441H associated with PD evolving to PSP. Neurology, 67(8):1518-1519.
SPILLANTINI, M.G., T.D., BIRD, B., GHETTI (1998): Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies. Brain Pathol., 8(2):387-402.
SPILLANTINI, M.G., M., GOEDERT (1998): Tau protein pathology in neurodegenerative diseases. Trends Neurosci., 21(10):428-433.
SUN, Z., H., JIANG, B., JIAO, X., HOU, L., SHEN, K., XIA, B., TANG (2015): C9orf72 hexanucleotide expansion analysis in Chinese patients with multiple system atrophy. Parkinsonism Relat. Disord., 21(7):811-812.
THEUNS, J., A., VERSTRAETEN, K., SLEEGERS, E., WAUTERS, I., GIJSELINCK, S., SMOLDERS, D., CROSIERS, E., CORSMIT, E., ELINCK, M., SHARMA, R., KRÜGER, S., LESAGE, A., BRICE, S.J., CHUNG, M.J., KIM, Y.J., KIM, O.A., ROSS, Z.K., WSZOLEK, E., ROGAEVA, Z., XI, A.E,. LANG, C., KLEIN, A., WEISSBACH, G.D., MELLICK, P.A., SILBURN, G.M., HADJIGEORGIOU, E., DARDIOTIS, N., HATTORI, K., OGAKI, E.K., TAN, Y., ZHAO, J., AASLY, E.M., VALENTE, S., PETRUCCI, G., ANNESI, A., QUATTRONE, C., FERRARESE, L., BRIGHINA, A., DEUTSCHLÄNDER, A., PUSCHMANN, C., NILSSON, G., GARRAUX, M.S., LEDOUX, R.F., PFEIFFER, M., BOCZARSKA-JEDYNAK, G., OPALA, D.M., MARAGANORE, S., ENGELBORGHS, P.P., DE DEYN, P., CRAS, M., CRUTS, C., VAN BROECKHOVEN, GEO-PD CONSORTIUM (2014): Global investigation and meta-analysis of the C9orf72 (G4C2) n repeat in Parkinson disease. Neurology, 83(21):1906-1913.
TICOZZI, N., C., TILOCA, D., CALINI, S., GAGLIARDI, A., ALTIERI, C., COLOMBRITA, C., CEREDA, A., RATTI, G., PEZZOLI, B., BORRONI, S., GOLDWURM, A., PADOVANI, V., SILANI (2014): C9orf72 repeat expansions are restricted to the ALS-FTD spectrum. Neurobiol. Aging., 35(4):936.e13-e17.
WENNING, G.K., F., GESER, M., STAMPFER-KOUNTCHEV, F., TISON (2003): Multiple system atrophy: an update. Mov. Disord., 18 Suppl 6:S34-42.
WILKE, C., J.K., POMPER, S., BISKUP, C., PUSKÁS, D., BERG, M., SYNOFZIK (2016): Atypical parkinsonism in C9orf72 expansions: a case report and systematic review of 45 cases from the literature. J. Neurol., 263(3):558-574.
YEH, T.H., S.C., LAI, Y.H., WENG, H.C., KUO, Y.H., WU-CHOU, C.L., HUANG, R.S., CHEN, H.C., CHANG, B., TRAYNOR, C.S., LU (2013): Screening for C9orf72 repeat expansions in parkinsonian syndromes. Neurobiol. Aging., 34(4):1311.e3-e4.
ZIMPRICH, A., S., BISKUP, P., LEITNER, P., LICHTNER, M., FARRER, S., LINCOLN, J., KACHERGUS, M., HULIHAN, R.J., UITTI, D.B., CALNE, A.J., STOESSL, R.F., PFEIFFER, N., PATENGE, I.C., CARBAJAL, P., VIEREGGE, F., ASMUS, B., MÜLLER-MYHSOK, D.W., DICKSON, T., MEITINGER, T.M., STROM, Z.K., WSZOLEK, T., GASSER (2004): Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron., 44(4):601-607.