Advertisement

Neurological Sciences

, Volume 40, Issue 10, pp 2111–2118 | Cite as

A novel S379A TARDBP mutation associated to late-onset sporadic ALS

  • Teresa Sprovieri
  • Carmine UngaroEmail author
  • Benedetta Perrone
  • Giuseppina Daniela Naimo
  • Rossella Spataro
  • Sebastiano Cavallaro
  • Vincenzo La Bella
  • Francesca Luisa Conforti
Original Article

Abstract

Since 2008, several groups have reported a lot of dominant mutations in TARDBP gene as a primary cause of Amyotrophic lateral sclerosis (ALS). Mutations in TARDBP gene are responsible for 4–5% of familial ALS (fALS) and nearly 1% of sporadic ALS (sALS). To date, over 50 dominant mutations were found in TDP-43 in both familial and sporadic ALS patients, most of which were missense mutations in the C-terminal glycine-rich region. Herein, we describe the clinical and genetic analysis of an Italian non-familial ALS patient with a late onset and a rapid disease progression, which led to the discovery of a novel TARDBP mutation. After neurological evaluation, molecular investigation highlighted the heterozygous substitution in exon 6 of TARDBP gene (S379A), which has previously neither been described nor reported in the ALS database. Several evidences supported the S379A mutation as causative in our patient: (a) it was neither found in ExAC nor 1000G and it was absent in our database of control subjects; (b) the position of the mutation involves an evolutionarily highly conserved residue; (c) two different amino acid substitutions in the same 379 codon were already reported in Swedish and Italian fALS cases, supporting the critical role of this codon for the protein function. The identification of this novel mutation enlarges the number of TARDBP mutations in ALS patients.

Keywords

ALS TARDBP TDP-43 Mutation 

Notes

Acknowledgements

The authors gratefully acknowledge Ariangela Belvedere, Walter Carpino, Benedetto Bruno, Patrizia Rizzuto, Tiziana Martire, and Angelo Bagalà for their administrative and technical support.

Authors’ contributions

Analysis, acquisition, and interpretation of data: CU, TS, BP, and GDN. Provision of patient samples and collection of clinical data: RS and VLB. Drafting and revising of manuscript: FLC, CU, TS, SB, VLB. Study conception and design: FLC.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all patients.

References

  1. 1.
    Nishiyama A, Niihori T, Warita H, Izumi R, Akiyama T, Kato M, Suzuki N, Aoki Y, Aoki M (2017) Comprehensive targeted next-generation sequencing in Japanese familial amyotrophic lateral sclerosis. Neurobiol Aging 53:194.e1–194.e8.  https://doi.org/10.1016/j.neurobiolaging.2017.01.004 CrossRefGoogle Scholar
  2. 2.
    Bonafede R, Mariotti R (2017) ALS pathogenesis and therapeutic approaches: the role of mesenchymal stem cells and extracellular vesicles. Front Cell Neurosci 11:80.  https://doi.org/10.3389/fncel.2017.00080 eCollection 2017. ReviewCrossRefGoogle Scholar
  3. 3.
    Murray ME, DeJesus-Hernandez M, Rutherford NJ, Baker M, Duara R, Graff-Radford NR, Wszolek ZK, Ferman TJ, Josephs KA, Boylan KB, Rademakers R, Dickson DW (2011) Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72. Acta Neuropathol 122(6):673–690.  https://doi.org/10.1007/s00401-011-0907-y CrossRefGoogle Scholar
  4. 4.
    Renton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Hölttä-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chiò A, Restagno G, Borghero G, Sabatelli M, ITALSGEN Consortium HD, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ (2011) Traynor BJ. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72(2):257–268.  https://doi.org/10.1016/j.neuron.2011.09.010. CrossRefGoogle Scholar
  5. 5.
    Rosen DR, Sapp P, O'Regan J, McKenna-Yasek D, Schlumpf KS, Haines JL, Gusella JF, Horvitz HR, Brown RH Jr (1994) Genetic linkage analysis of familial amyotrophic lateral sclerosis using human chromosome 21 microsatellite DNA markers. Am J Med Genet 51(1):61–69CrossRefGoogle Scholar
  6. 6.
    Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, Davis A, Gilchrist J, Kasarskis EJ, Munsat T, Valdmanis P, Rouleau GA, Hosler BA, Cortelli P, de Jong PJ, Yoshinaga Y, Haines JL, Pericak-Vance MA, Yan J, Ticozzi N, Siddique T, McKenna-Yasek D, Sapp PC, Horvitz HR, Landers JE, Brown RH Jr (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323(5918):1205–1208.  https://doi.org/10.1126/science.1166066 CrossRefGoogle Scholar
  7. 7.
    Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, Ackerley S, Durnall JC, Williams KL, Buratti E, Baralle F, de Belleroche J, Mitchell JD, Leigh PN, Al-Chalabi A, Miller CC, Nicholson G, Shaw CE (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319(5870):1668–1672.  https://doi.org/10.1126/science.1154584 CrossRefGoogle Scholar
  8. 8.
    Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Suzuki N, Aoki M, Kawata A, Hirai T, Kato T, Ogasawara K, Hirano A, Takumi T, Kusaka H, Hagiwara K, Kaji R, Kawakami H (2010) Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465(7295):223–226.  https://doi.org/10.1038/nature08971 CrossRefGoogle Scholar
  9. 9.
    Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, Ajroud K, Sufit RL, Haines JL, Mugnaini E, Pericak-Vance MA, Siddique T (2011) Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477(7363):211–215.  https://doi.org/10.1038/nature10353 CrossRefGoogle Scholar
  10. 10.
    Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Kurppa K, Moritoyo H, Belzil VV, Dion PA, Higasa K, Doi K, Ishiura H, Mitsui J, Date H, Ahsan B, Matsukawa T, Ichikawa Y, Moritoyo T, Ikoma M, Hashimoto T, Kimura F, Murayama S, Onodera O, Nishizawa M, Yoshida M, Atsuta N, Sobue G, JaCALS FJA, Williams KL, Blair IP, Nicholson GA, Gonzalez-Perez P, Brown RH Jr, Nomoto M, Elenius K, Rouleau GA, Fujiyama A, Morishita S, Goto J, Tsuji S (2013) ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19. Am J Hum Genet 93(5):900–905.  https://doi.org/10.1016/j.ajhg.2013.09.008 CrossRefGoogle Scholar
  11. 11.
    Lagier-Tourenne C, Polymenidou M, Hutt KR, Vu AQ, Baughn M, Huelga SC, Clutario KM, Ling SC, Liang TY, Mazur C, Wancewicz E, Kim AS, Watt A, Freier S, Hicks GG, Donohue JP, Shiue L, Bennett CF, Ravits J, Cleveland DW, Yeo GW (2012) Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. Nat Neurosci 15(11):1488–1497.  https://doi.org/10.1038/nn.3230 CrossRefGoogle Scholar
  12. 12.
    Abrahams S, Newton J, Niven E, Foley J, Bak TH (2014) Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener 15(1–2):9–14.  https://doi.org/10.3109/21678421.2013.805784 CrossRefGoogle Scholar
  13. 13.
    Chiò A, Calvo A, Moglia C, Restagno G, Ossola I, Brunetti M, Montuschi A, Cistaro A, Ticca A, Traynor BJ, Schymick JC, Mutani R, Marrosu MG, Murru MR, Borghero G (2010) Amyotrophic lateral sclerosis-frontotemporal lobar dementia in 3 families with p.Ala382Thr TARDBP mutations. Arch Neurol 67(8):1002–1009.  https://doi.org/10.1001/archneurol.2010.173 CrossRefGoogle Scholar
  14. 14.
    Freibaum BD, Chitta RK, High AA, Taylor JP (2010) Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. J Proteome Res 9(2):1104–1120.  https://doi.org/10.1021/pr901076y CrossRefGoogle Scholar
  15. 15.
    Russo A, Scardigli R, La Regina F, Murray ME, Romano N, Dickson DW, Wolozin B, Cattaneo A, Ceci M (2017) Increased cytoplasmic TDP-43 reduces global protein synthesis by interacting with RACK1 on polyribosomes. Hum Mol Genet 26(8):1407–1418.  https://doi.org/10.1093/hmg/ddx035 CrossRefGoogle Scholar
  16. 16.
    Dong QX, Zhu J, Liu SY, Yu XL, Liu RT (2018) An oligomer-specific antibody improved motor function and attenuated neuropathology in the SOD1-G93A transgenic mouse model of ALS. Int Immunopharmacol 65:413–421.  https://doi.org/10.1016/j.intimp.2018.10.032 CrossRefGoogle Scholar
  17. 17.
    Ravanidis S, Kattan FG, Doxakis E (2018) Unraveling the pathways to neuronal homeostasis and disease: mechanistic insights into the role of RNA-binding proteins and associated factors. Int J Mol Sci 19(8).  https://doi.org/10.3390/ijms19082280
  18. 18.
    Sun Y, Chakrabartty A (2017) Phase to phase with TDP-43. Biochemistry 56(6):809–823.  https://doi.org/10.1021/acs.biochem.6b01088 CrossRefGoogle Scholar
  19. 19.
    Millecamps S, Salachas F, Cazeneuve C, Gordon P, Bricka B, Camuzat A, Guillot-Noël L, Russaouen O, Bruneteau G, Pradat PF, Le Forestier N, Vandenberghe N, Danel-Brunaud V, Guy N, Thauvin-Robinet C, Lacomblez L, Couratier P, Hannequin D, Seilhean D, Le Ber I, Corcia P, Camu W, Brice A, Rouleau G, LeGuern E, Meininger V (2010) SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis:genotype-phenotype correlations. J Med Genet 47:554–560CrossRefGoogle Scholar
  20. 20.
    Pamphlett R, Kum Jew S (2008) TDP-43 inclusions do not protect motor neurons from sporadic ALS. Acta Neuropathol 116(2):221–222.  https://doi.org/10.1007/s00401-008-0392-0 CrossRefGoogle Scholar
  21. 21.
    Tamaoka A, Arai M, Itokawa M, Arai T, Hasegawa M, Tsuchiya K, Takuma H, Tsuji H, Ishii A, Watanabe M, Takahashi Y, Goto J, Tsuji S, Akiyama H (2010) TDP-43 M337V mutation in familial amyotrophic lateral sclerosis in Japan. Intern Med 49(4):331–334CrossRefGoogle Scholar
  22. 22.
    Xiong HL, Wang JY, Sun YM, Wu JJ, Chen Y, Qiao K, Zheng QJ, Zhao GX, Wu ZY (2010) Association between novel TARDBP mutations and Chinese patients with amyotrophic lateral sclerosis. BMC Med Genet 11:8.  https://doi.org/10.1186/1471-2350-11-8 CrossRefGoogle Scholar
  23. 23.
    Therrien M, Dion PA, Rouleau GA (2016) ALS: recent developments from genetics studies. Curr Neurol Neurosci Rep 16(6):59.  https://doi.org/10.1007/s11910-016-0658-1. ReviewCrossRefGoogle Scholar
  24. 24.
    Siciliano M, Trojano L, Trojsi F, Greco R, Santoro M, Basile G, Piscopo F, D'Iorio A, Patrone M, Femiano C, Monsurrò M, Tedeschi G, Santangelo G (2017) Edinburgh cognitive and behavioural ALS screen (ECAS)-Italian version: regression based norms and equivalent scores. Neurol Sci 38(6):1059–1068.  https://doi.org/10.1007/s10072-017-2919-4 CrossRefGoogle Scholar
  25. 25.
    Brooks BR, Miller RG, Swash M, Munsat TL (2000) World Federation of Neurology Research Group on motor neuron diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1(5):293–299 ReviewCrossRefGoogle Scholar
  26. 26.
    Kimura F, Fujimura C, Ishida S, Nakajima H, Furutama D, Uehara H, Shinoda K, Sugino M, Hanafusa T (2006) Progression rate of ALSFRS-R at the time of diagnosis predicts survival time in ALS. Neurology 66:265–267CrossRefGoogle Scholar
  27. 27.
    Winton MJ, Van Deerlin VM, Kwong LK, Yuan W, Wood EM, Yu CE, Schellenberg GD, Rademakers R, Caselli R, Karydas A, Trojanowski JQ, Miller BL, Lee VM (2008) A90V TDP-43 variant results in the aberrant localization of TDP-43 in vitro. FEBS Lett 582(15):2252–2256.  https://doi.org/10.1016/j.febslet.2008.05.024 CrossRefGoogle Scholar
  28. 28.
    Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard JP, Lacomblez L, Pochigaeva K, Salachas F, Pradat PF, Camu W, Meininger V, Dupre N, Rouleau GA (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40(5):572–574.  https://doi.org/10.1038/ng.132 CrossRefGoogle Scholar
  29. 29.
    Corrado L, Ratti A, Gellera C, Buratti E, Castellotti B, Carlomagno Y, Ticozzi N, Mazzini L, Testa L, Taroni F, Baralle FE, Silani V, D'Alfonso S (2009) High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum Mutat 30(4):688–694.  https://doi.org/10.1002/humu.20950 CrossRefGoogle Scholar
  30. 30.
    Van Deerlin VM, Leverenz JB, Bekris LM, Bird TD, Yuan W, Elman LB, Clay D, Wood EM, Chen-Plotkin AS, Martinez-Lage M, Steinbart E, McCluskey L, Grossman M, Neumann M, Wu IL, Yang WS, Kalb R, Galasko DR, Montine TJ, Trojanowski JQ, Lee VM, Schellenberg GD, Yu CE (2008) TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 7(5):409–416.  https://doi.org/10.1016/S1474-4422(08)70071-1 CrossRefGoogle Scholar
  31. 31.
    Chiang HH, Andersen PM, Tysnes OB, Gredal O, Christensen PB, Graff C (2012) Novel TARDBP mutations in Nordic ALS patients. J Hum Genet 57(5):316–319.  https://doi.org/10.1038/jhg.2012.24 CrossRefGoogle Scholar
  32. 32.
    van Blitterswijk M, van Es MA, Hennekam EA, Dooijes D, van Rheenen W, Medic J, Bourque PR, Schelhaas HJ, van der Kooi AJ, de Visser M, de Bakker PI, Veldink JH, van den Berg LH (2012) Evidence for an oligogenic basis of amyotrophic lateral sclerosis. Hum Mol Genet 21(17):3776–3784.  https://doi.org/10.1093/hmg/dds199 CrossRefGoogle Scholar
  33. 33.
    Lattante S, Conte A, Zollino M, Luigetti M, Del Grande A, Marangi G, Romano A, Marcaccio A, Meleo E, Bisogni G, Rossini PM, Sabatelli M (2012) Contribution of major amyotrophic lateral sclerosis genes to the etiology of sporadic disease. Neurology 79(1):66–72.  https://doi.org/10.1212/WNL.0b013e31825dceca CrossRefGoogle Scholar
  34. 34.
    Lemmens R, Race V, Hersmus N, Matthijs G, Van Den Bosch L, Van Damme P, Dubois B, Boonen S, Goris A, Robberecht W (2009) TDP-43 M311V mutation in familial amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 80(3):354–355.  https://doi.org/10.1136/jnnp.2008.157677 CrossRefGoogle Scholar
  35. 35.
    Fujita Y, Ikeda M, Yanagisawa T, Senoo Y, Okamoto K (2011) Different clinical and neuropathologic phenotypes of familial ALS with A315E TARDBP mutation. Neurology 77(15):1427–1431.  https://doi.org/10.1212/WNL.0b013e318232ab87 CrossRefGoogle Scholar
  36. 36.
    Gitcho MA, Baloh RH, Chakraverty S, Mayo K, Norton JB, Levitch D, Hatanpaa KJ, White CL 3rd, Bigio EH, Caselli R, Baker M, Al-Lozi MT, Morris JC, Pestronk A, Rademakers R, Goate AM, Cairns NJ (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63(4):535–538.  https://doi.org/10.1002/ana.21344 CrossRefGoogle Scholar
  37. 37.
    Kirby J, Goodall EF, Smith W, Highley JR, Masanzu R, Hartley JA, Hibberd R, Hollinger HC, Wharton SB, Morrison KE, Ince PG, McDermott CJ, Shaw PJ (2010) Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis. Neurogenetics 11(2):217–225.  https://doi.org/10.1007/s10048-009-0218-9 CrossRefGoogle Scholar
  38. 38.
    Bäumer D, Parkinson N, Talbot K (2009) TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but absence of copy number variation. J Neurol Neurosurg Psychiatry 80(11):1283–1285.  https://doi.org/10.1136/jnnp.2008.166512 CrossRefGoogle Scholar
  39. 39.
    Yokoseki A, Shiga A, Tan CF, Tagawa A, Kaneko H, Koyama A, Eguchi H, Tsujino A, Ikeuchi T, Kakita A, Okamoto K, Nishizawa M, Takahashi H, Onodera O (2008) TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol 63(4):538–542.  https://doi.org/10.1002/ana.21392 CrossRefGoogle Scholar
  40. 40.
    Rutherford NJ, Zhang YJ, Baker M, Gass JM, Finch NA, Xu YF, Stewart H, Kelley BJ, Kuntz K, Crook RJ, Sreedharan J, Vance C, Sorenson E, Lippa C, Bigio EH, Geschwind DH, Knopman DS, Mitsumoto H, Petersen RC, Cashman NR, Hutton M, Shaw CE, Boylan KB, Boeve B, Graff-Radford NR, Wszolek ZK, Caselli RJ, Dickson DW, Mackenzie IR, Petrucelli L, Rademakers R (2008) Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet 4(9):e1000193.  https://doi.org/10.1371/journal.pgen.1000193 CrossRefGoogle Scholar
  41. 41.
    Kühnlein P, Sperfeld AD, Vanmassenhove B, Van Deerlin V, Lee VM, Trojanowski JQ, Kretzschmar HA, Ludolph AC, Neumann M (2008) Two German kindreds with familial amyotrophic lateral sclerosis due to TARDBP mutations. Arch Neurol 65(9):1185–1189.  https://doi.org/10.1001/archneur.65.9.1185 CrossRefGoogle Scholar
  42. 42.
    Iida A, Kamei T, Sano M, Oshima S, Tokuda T, Nakamura Y, Ikegawa S (2012) Large-scale screening of TARDBP mutation in amyotrophic lateral sclerosis in Japanese. Neurobiol Aging 33(4):786–790.  https://doi.org/10.1016/j.neurobiolaging.2010.06.017 CrossRefGoogle Scholar
  43. 43.
    Daoud H, Valdmanis PN, Kabashi E, Dion P, Dupré N, Camu W, Meininger V, Rouleau GA (2009) Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J Med Genet 46(2):112–114.  https://doi.org/10.1136/jmg.2008.062463 CrossRefGoogle Scholar
  44. 44.
    De Marco G, Lupino E, Calvo A, Moglia C, Buccinnà B, Grifoni S, Ramondetti C, Lomartire A, Rinaudo MT, Piccinini M, Giordana MT, Chiò A (2011) Cytoplasmic accumulation of TDP-43 in circulating lymphomonocytes of ALS patients with and without TARDBP mutations. Acta Neuropathol 121(5):611–622.  https://doi.org/10.1007/s00401-010-0786-7 CrossRefGoogle Scholar
  45. 45.
    Cady J, Allred P, Bali T, Pestronk A, Goate A, Miller TM, Mitra RD, Ravits J, Harms MB, Baloh RH (2015) Amyotrophic lateral sclerosis onset is influenced by the burden of rare variants in known amyotrophic lateral sclerosis genes. Ann Neurol 77(1):100–113.  https://doi.org/10.1002/ana.24306 CrossRefGoogle Scholar
  46. 46.
    Conforti FL, Sproviero W, Simone IL, Mazzei R, Valentino P, Ungaro C, Magariello A, Patitucci A, La Bella V, Sprovieri T, Tedeschi G, Citrigno L, Gabriele AL, Bono F, Monsurrò MR, Muglia M, Gambardella A, Quattrone A (2011) TARDBP gene mutations in south Italian patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 82(5):587–588.  https://doi.org/10.1136/jnnp.2009.198309 CrossRefGoogle Scholar
  47. 47.
    Ticozzi N, LeClerc AL, van Blitterswijk M, Keagle P, McKenna-Yasek DM, Sapp PC, Silani V, Wills AM, Brown RH Jr, Landers JE (2011) Mutational analysis of TARDBP in neurodegenerative diseases. Neurobiol Aging 32(11):2096–2099.  https://doi.org/10.1016/j.neurobiolaging.2009.11.018 CrossRefGoogle Scholar
  48. 48.
    Huang R, Fang DF, Ma MY, Guo XY, Zhao B, Zeng Y, Zhou D, Yang Y, Shang HF (2012) TARDBP gene mutations among Chinese patients with sporadic amyotrophic lateral sclerosis. Neurobiol Aging 33(5):1015.e1–1015.e6.  https://doi.org/10.1016/j.neurobiolaging.2010.07.007 CrossRefGoogle Scholar

Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • Teresa Sprovieri
    • 1
  • Carmine Ungaro
    • 1
    Email author
  • Benedetta Perrone
    • 1
  • Giuseppina Daniela Naimo
    • 1
  • Rossella Spataro
    • 2
  • Sebastiano Cavallaro
    • 1
  • Vincenzo La Bella
    • 3
  • Francesca Luisa Conforti
    • 4
  1. 1.Institute of Neurological SciencesNational Research CouncilMangoneItaly
  2. 2.IRCCS Centro Neurolesi “Bonino Pulejo”PalermoItaly
  3. 3.ALS Clinical Research Center and Laboratory of Neurochemistry, Department of Experimental Biomedicine and Clinical NeurosciencesUniversity of PalermoPalermoItaly
  4. 4.Department of Pharmacy and Health and Nutritional SciencesUniversity of CalabriaRendeItaly

Personalised recommendations