Advertisement

Toxicology and Environmental Health Sciences

, Volume 5, Issue 3, pp 113–130 | Cite as

Genetic factors in frontotemporal dementia: A review

  • Lingyan Shen
  • Eva Bagyinszky
  • Young Chul Youn
  • Seong Soo A. AnEmail author
  • SangYun KimEmail author
Mini Review

Abstract

Frontotemporal dementia (FTD) is the second most common form of neurogenerative dementia, following Alzheimer’s disease (AD). FTD is a clinically and phenotypically heterogeneous disorder, which occurs mostly in younger patients under 60 years of age. Several genes were described to be involved in FTD: progranulin (PGRN), microtubule-associated protein tau (MAPT), chromosome 9 open reading frame 72 (C9orf72), fused in sarcoma (FUS), TAR DNA binding protein-43 (TARDBP), valosin-containing protein (VCP), and charged multivesicular body protein 2B (CHMP 2B). Genome-wide association studies (GWAS) identified additional putative FTD risk factor genes, such as transmembrane protein 106B (TMEM106B) or ubiquilin-2 (UBQLN2). Improvements in genetic analysis could enhance the differential diagnosis for neurodegenerative disorders, especially FTD. This review summarized the FTD-associated genes, mutations and the latest methods for genetic analysis.

Keywords

FTD Mutation Dementia PGRN MAPT C9orf72 TARDBP VCP FUS CHMP2B 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Graham, A. et al. Pathologically proven frontotemporal dementia presenting with severe amnesia. Brain 128, 597–605 (2005).PubMedGoogle Scholar
  2. 2.
    Chan, D. K., Reutens, S., Liu, D. K. & Chan, R. O. Frontotemporal dementia-features, diagnosis and management. Aust. Fam. Physician 40, 968–972 (2011).PubMedGoogle Scholar
  3. 3.
    Ratnavalli, E., Brayne, C., Dawson, K. & Hodges, J. R. The prevalence of frontotemporal dementia. Neurology 58, 1615–1621 (2002).PubMedGoogle Scholar
  4. 4.
    Neary, D., Snowden, J. & Mann, D. Frontotemporal dementia. Lancet Neurol. 4, 771–780 (2005).PubMedGoogle Scholar
  5. 5.
    Seltman, R. E. & Matthews, B. R. Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management. CNS Drugs 26, 841–870 (2012).PubMedGoogle Scholar
  6. 6.
    Leyton, C. E. & Hodges, J. R. Frontotemporal dementias: Recent advances and current controversies. Ann. Indian. Acad. Neurol. 13, 74–80 (2010).Google Scholar
  7. 7.
    Snowden, J. S., Neary, D. & Mann, D. M. Frontotemporal dementia. Br. J. Psychiatry 180, 140–143 (2002).PubMedGoogle Scholar
  8. 8.
    Jellinger, K. A. Neuropathological aspects of Alzheimer disease, Parkinson disease and frontotemporal dementia, Neurodegener. Dis. 5, 118–121 (2008).PubMedGoogle Scholar
  9. 9.
    Homepage of Dementia EEG analysis, Tutoruials for the Mentis Cura, Neurodiagnostic Aid, http://www.mentiscura.is/.
  10. 10.
    Jicha, G. A. Medical management of frontotemporal dementias: the importance of the caregiver in symptom assessment and guidance of treatment strategies. Mol. Neurosci. 45, 713–723 (2011).Google Scholar
  11. 11.
    Jicha, G. A. & Nelson, P. T. Management of frontotemporal dementia: targeting symptom management in such a heterogeneous disease requires a wide range of therapeutic options. Neurodegener. Dis. Manag. 1, 141–156 (2011).PubMedGoogle Scholar
  12. 12.
    Ferrari, R., Hardy, J. & Momeni, P. Frontotemporal dementia: from Mendelian genetics towards genome wide association studies. J. Mol. Neurosci. 45, 500–515 (2011).PubMedGoogle Scholar
  13. 13.
    Homepage of AD and FTD mutation database: http://www.molgen.ua.ac.be/admutations.
  14. 14.
    Rademakers, R. et al. Tau negative frontal lobe dementia at 17q21: significant finemapping of the candidate region to a 4.8 cM interval. Mol. Psychiatry 7, 1064–1074 (2002).PubMedGoogle Scholar
  15. 15.
    Arai, T. et al. TDP-43 is a component of ubiquitinpositive taunegative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 351, 602–611 (2006).PubMedGoogle Scholar
  16. 16.
    Vance, C. et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208–1211 (2009).PubMedGoogle Scholar
  17. 17.
    Daniel, R., He, Z., Carmichael, K. P., Halper, J. & Bateman, A. Cellular localization of gene expression for progranulin. J. Histochem. Cytochem. 48, 999–1009 (2000).PubMedGoogle Scholar
  18. 18.
    Van Damme, P. V. et al. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J. Cell. Biol. 181, 37–41 (2008).PubMedGoogle Scholar
  19. 19.
    Gijselinck, I., Van Broeckhoven, C. & Cruts, M. Granulin mutations associated with frontotemporal lobar degeneration and related disorders: An update. Human Mutation 29, 1373–1386 (2008).PubMedGoogle Scholar
  20. 20.
    Brouwers, N. et al. Alzheimer and Parkinson diagnoses in progranulin null mutation carriers in an extended founder family. Arch. Neurol. 64, 1436–1446 (2007).PubMedGoogle Scholar
  21. 21.
    Baker, M. et al. Mutations in progranulin cause taunegative frontotemporal dementia linked to chromosome 17. Nature 442, 916–919 (2006).PubMedGoogle Scholar
  22. 22.
    Le Ber, I. et al. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study. Brain 131, 732–746 (2008).PubMedGoogle Scholar
  23. 23.
    Gass, J. et al. Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum. Mol. Gen. 15, 2988–3001 (2006).PubMedGoogle Scholar
  24. 24.
    Brouwers, N. et al. Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease. Neurology 71, 656–664 (2008).PubMedGoogle Scholar
  25. 25.
    Cruts, M. et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442, 920–924 (2006).PubMedGoogle Scholar
  26. 26.
    Mukherjee, O. et al. Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia. Human Mutation 29, 512–521 (2008).PubMedGoogle Scholar
  27. 27.
    Shankaran, S. S. et al. Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitinimmunoreactive inclusions reduce progranulin production and secretion. J. Biol. Chem. 283, 1744–1753 (2008).PubMedGoogle Scholar
  28. 28.
    Van der Zee, J. et al. Belgian ancestral haplotype harbors a highly prevalent mutation for 17q21-linked tau-negative FTLD. Brain 129, 841–852 (2006).PubMedGoogle Scholar
  29. 29.
    Rademakers, R. et al. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum. Mol. Genet. 17, 3631–3642 (2008).PubMedGoogle Scholar
  30. 30.
    Rollinson, S. et al. No association of PGRN 3′-UTR rs5848 in frontotemporal lobar degeneration. Neurobiol Aging 32, 754–755 (2009).PubMedGoogle Scholar
  31. 31.
    Rovelet-Lecrux, A. et al. Deletion of the progranulin gene in patients with frontotemporal lobar degeneration or Parkinson disease. Neurobiol. Dis. 31, 41–45 (2008).PubMedGoogle Scholar
  32. 32.
    López de Munain, A. et al. Mutations in Progranulin Gene: Clinical, Pathological, and Ribonucleic Acid Expression Findings. Biol. Psychiatry 63, 946–952 (2008).PubMedGoogle Scholar
  33. 33.
    Guerreiro, R. J. et al. Novel progranulin mutation: Screening for PGRN mutations in a Portuguese series of FTD/CBS cases. Mov. Disord. 23, 1269–1273 (2008).PubMedGoogle Scholar
  34. 34.
    Guerreiro, R. J., Washecka, N., Hardy, J. & Singleton, A. A thorough assessment of benign genetic variability in GRN and MAPT. Hum. Mutat. 31, 1126–1140 (2010).Google Scholar
  35. 35.
    van der Zee, J. et al. Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementia. Hum. Mutat. 28, 416 (2007).PubMedGoogle Scholar
  36. 36.
    Cortini, F. et al. Novel exon 1 progranulin gene variant in Alzheimer’s disease. Eur. J. Neurol. 15, 1111–1117 (2008).PubMedGoogle Scholar
  37. 37.
    Kelley, B. J. et al. Alzheimer disease-like phenotype associated with the c.154delA mutation in progranulin. Arch. Neurol. 67, 171–177 (2010).PubMedGoogle Scholar
  38. 38.
    Skoglund, L. et al. Mutation analysis of the progranulin gene in a Scandinavian frontotemporal dementia population. Neurodeg. Dis. 4, 38 (2007).Google Scholar
  39. 39.
    Bronner, I. F. et al. Progranulin mutations in Dutch familial frontotemporal lobar degeneration. Eur. J. Hum. Genet. 15, 369–374 (2007).PubMedGoogle Scholar
  40. 40.
    Van Deerlin, V. M. et al. Clinical, genetic, and pathologic characteristics of patients with frontotemporal dementia and progranulin mutations. Arch. Neurol. 64, 1148–1153 (2007).PubMedGoogle Scholar
  41. 41.
    Sleegers, K. et al. Progranulin genetic variability contributes to amyotrophic lateral sclerosis. Neurology 71, 253–259 (2008).PubMedGoogle Scholar
  42. 42.
    Schymick, J. et al. Progranulin mutations and ALS or ALS-FTD phenotypes. J. Neurol. Neurosurg. Psychiatry 78, 754–756 (2007).PubMedGoogle Scholar
  43. 43.
    Pickering-Brown, S. M. et al. Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations. Brain 131, 721–731 (2008).PubMedGoogle Scholar
  44. 44.
    Finch, N. et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 132, 583–591 (2009).PubMedGoogle Scholar
  45. 45.
    Beck, J. et al. A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series. Brain 131, 706–720 (2008).PubMedGoogle Scholar
  46. 46.
    Benussi, L. et al. Progranulin Leu271LeufsX10 is one of the most common FTLD and CBS associated mutations worldwide. Neurobiol. Dis. 33, 379–385 (2008).PubMedGoogle Scholar
  47. 47.
    Spina, S., Murrell, J. R., Vidal, R. & Ghetti, B. Neuropathologic and genetic characterization of frontotemporal lobar degeneration with Ubiquitin-and/or Tdp-43-positive inclusions: A large series. Alzheimer’s & Dementia 4Suppl 2, 431 (2008).Google Scholar
  48. 48.
    Steinbach, P. Personal Communication (2009).Google Scholar
  49. 49.
    Schlachetzki, J. C. et al. Frequency of progranulin mutations in a German cohort of 79 frontotemporal dementia patients. J. Neurol. 256, 2043–2051 (2009).PubMedGoogle Scholar
  50. 50.
    Ghetti, B. et al. In vivo and postmortem clinicoanatomical correlations in frontotemporal dementia and parkinsonism linked to chromosome 17. Neurodegener. Dis. 5, 215–217 (2008).PubMedGoogle Scholar
  51. 51.
    Lladó, A. et al. Late-onset frontotemporal dementia associated with a novel PGRN mutation. J. Neural Transm. 114, 1051–1054 (2007).PubMedGoogle Scholar
  52. 52.
    Bruni, A. C. et al. Heterogeneity within a large kindred with frontotemporal dementia: a novel progranulin mutation. Neurology 69, 140–147 (2007).PubMedGoogle Scholar
  53. 53.
    Cruchaga, C. et al. Cortical Atrophy and Language Network Reorganization Associated with a Novel Progranulin Mutation. Cereb. Cortex 19, 1751–1760 (2009).PubMedGoogle Scholar
  54. 54.
    Wong, S. H., Lecky, B. R. & Steiger, M. J. Parkinsonism and impulse control disorder: presentation of a new progranulin gene mutation. Mov. Disord. 24, 618–619 (2009).PubMedGoogle Scholar
  55. 55.
    Mackenzie, I. R. et al. Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype. Acta Neuropathol. 112, 539–549 (2006).PubMedGoogle Scholar
  56. 56.
    Rosso, S. M. et al. Familial frontotemporal dementia with ubiquitin-positive inclusions is linked to chromosome 17q21–22. Brain 124, 1948–1957 (2001).PubMedGoogle Scholar
  57. 57.
    Rohrer, J. D. et al. Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by progranulin and tau mutations. Neuroimage 53, 1070–1076 (2010).PubMedGoogle Scholar
  58. 58.
    Goedert, M. Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci. 16, 460–465 (1993).PubMedGoogle Scholar
  59. 59.
    Hutton, M. et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702–705 (1998).PubMedGoogle Scholar
  60. 60.
    Poorkaj, P. et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815–825 (1998).PubMedGoogle Scholar
  61. 61.
    Dumanchin, C. et al. Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotempotal dementia and parkinsonism. Hum. Mol. Genet. 11, 1825–1829 (1998).Google Scholar
  62. 62.
    Spillantini, M. G. et al. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl. Acad. Sci. USA. 95, 7737–7741 (1998).PubMedGoogle Scholar
  63. 63.
    Kim, H. J. et al. Screening for MAPT and PGRN mutations in Korean patients with PSP/CBS/FTD. Parkinsonism Relat. Disord. 16, 305–306 (2010).PubMedGoogle Scholar
  64. 64.
    Whitwell, J. L. et al. Trajectories of brain and hippocampal atrophy in FTD with mutations in MAPT or GRN. Neurology 77, 393–398 (2011).PubMedGoogle Scholar
  65. 65.
    Rizzu, P. et al. High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am. J. Hum. Genet. 64, 414–421 (1999).PubMedGoogle Scholar
  66. 66.
    Hayashi, S. et al. Late-onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation. Ann. Neurol. 51, 525–530 (2002).PubMedGoogle Scholar
  67. 67.
    Poorkaj, P. et al. An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann. of Neurol. 52, 511–516 (2002).Google Scholar
  68. 68.
    Houlden, H. et al. Frequency of tau mutations in three series of non-Alzheimer’s degenerative dementia. Ann. Neurol. 46, 243–248 (1999).PubMedGoogle Scholar
  69. 69.
    Pickering-Brown, S. M. et al. Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. Brain 125, 732–751 (2002).PubMedGoogle Scholar
  70. 70.
    Rizzini, C. et al. Tau gene mutation K257T causes a tauopathy similar to Pick’s disease. J. Neuropathol. Exp. Neurol. 59, 990–1001 (2000).PubMedGoogle Scholar
  71. 71.
    Grover, A. et al. A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy. Exp. Neurol. 184, 131–140 (2003).PubMedGoogle Scholar
  72. 72.
    Kobayashi, T. et al. A novel L266V mutation of the tau gene causes frontotemporal dementia with a unique tau pathology. Ann. Neurol. 53, 133–137 (2003).PubMedGoogle Scholar
  73. 73.
    Malkani, R. et al. A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia. Neurobiol. Dis. 22, 401–403 (2006).PubMedGoogle Scholar
  74. 74.
    Kowalska, A. et al. Genetic analysis in patients with familial and sporadic frontotemporal dementia: two tau mutations in only familial cases and no association with apolipoprotein epsilon4. Dement. Geriatr. Cogn. Disord. 12, 387–392 (2001).PubMedGoogle Scholar
  75. 75.
    Poorkaj, P. et al. Frequency of tau gene mutations in familial and sporadic cases of non-Alzheimer dementia. Arch. Neurol. 58, 383–387 (2001).PubMedGoogle Scholar
  76. 76.
    Iseki, E. et al. Familial frontotemporal dementia and parkinsonism with a novel N296H mutation in exon 10 of the tau gene and a widespread tau accumulation in the glial cells. Acta Neuropathol. 102, 285–292 (2001).PubMedGoogle Scholar
  77. 77.
    Pastor, P. et al. Familial atypical progressive supranuclear palsy associated with homozigosity for the delN 296 mutation in the tau gene. Ann. of Neurol. 49, 263–267 (2001).Google Scholar
  78. 78.
    Lladó, A. et al. A novel MAPT mutation (P301T) associated with familial frontotemporal dementia. Eur. J. Neurol. 14, 9–10 (2007).Google Scholar
  79. 79.
    Morris, H. R. et al. The genetic and pathological classification of familial frontotemporal dementia. Arch. Neurol. 58, 1813–1816 (2001).PubMedGoogle Scholar
  80. 80.
    Miyamoto, K. et al. Familial frontotemporal dementia and parkinsonism with a novel mutation at an intron 10+11-splice site in the tau gene. Ann. Neurol. 50, 117–120 (2001).PubMedGoogle Scholar
  81. 81.
    Ros, R. et al. A new mutation of the tau gene, G303V, in early-onset familial progressive supranuclear palsy, Arch. Neurol. 62, 1444–1450 (2005).PubMedGoogle Scholar
  82. 82.
    Kobayashi, K. et al. KP1 expression of ghost Pick bodies, amyloid P-positive astrocytes and selective nigral degeneration in early onset Picks disease. Clin. Neuropathol. 18, 240–249 (1999).PubMedGoogle Scholar
  83. 83.
    Kovacs, G. G. et al. MAPT S305I mutation: implications for argyrophilic grain disease. Acta Neuropathol. 116, 103–118 (2008).PubMedGoogle Scholar
  84. 84.
    Spillantini, M. G. & Goedert, M. Tau mutations in familial frontotemporal dementia. Brain 123, 857–859 (2000).PubMedGoogle Scholar
  85. 85.
    Roks, G. et al. Mutation screening of the tau gene in patients with early-onset Alzheimer’s disease. Neurosci. Lett. 277, 137–139 (1999).PubMedGoogle Scholar
  86. 86.
    Rosso, S. M. et al. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain 126, 2016–2022 (2003).PubMedGoogle Scholar
  87. 87.
    Bird, T. Personal Communication (2005).Google Scholar
  88. 88.
    Zarranz, J. J. et al. A novel mutation (K317M) in the MAPT gene causes FTDP and motor neuron disease. Neurology 64, 1578–1585 (2005).PubMedGoogle Scholar
  89. 89.
    Neumann, M. et al. Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia. Neurogenetics 6, 91–95 (2005).PubMedGoogle Scholar
  90. 90.
    Pickering-Brown, S. M. et al. Frontotemporal dementia with Pick-type histology associated with Q336R mutation in the tau gene. Brain 127, 1415–1426 (2004).PubMedGoogle Scholar
  91. 91.
    Lippa, C. F. et al. Frontotemporal dementia with novel tau pathology and a Glu342Val tau mutation. Ann. Neurol. 48, 850–858 (2000).PubMedGoogle Scholar
  92. 92.
    Nicholl, D. J. et al. An English kindred with a novel recessive tauopathy and respiratory failure. Ann. Neurol. 54, 682–686 (2003).PubMedGoogle Scholar
  93. 93.
    Munoz, D. G., Ros, R., Fatas, M., Bermejo, F. & de Yebenes, J. G. Progressive nonfluent aphasia associated with a new mutation V363I in tau gene. Am. J. Alzheimers Dis. Other Demen. 22, 294–299 (2007).PubMedGoogle Scholar
  94. 94.
    Neumann, M. et al. Pick’s disease associated with the novel Tau gene mutation K369I. Ann. Neurol. 50, 503–513 (2001).PubMedGoogle Scholar
  95. 95.
    Murrell, J. R. et al. Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits. J. Neuropathol. Exp. Neurol. 58, 1207–1226 (1999).PubMedGoogle Scholar
  96. 96.
    Brice, A. Personal Communication (2005).Google Scholar
  97. 97.
    Giaccone, G. et al. Familial frontotemporal dementia associated with the novel MAPT mutation T427M. J. Neurol. 252, 1543–1545 (2005).PubMedGoogle Scholar
  98. 98.
    DeJesus-Hernandez, M. et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF 72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245–256 (2011).PubMedGoogle Scholar
  99. 99.
    Murray, M. E. et al. Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72. Acta Neuropathol. 122, 673–690 (2011).PubMedGoogle Scholar
  100. 100.
    Renton, A. E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, 257–268 (2011).PubMedGoogle Scholar
  101. 101.
    Rademakers, R. C9orf72 repeat expansions in patients with ALS and FTD, Lancet Neurol. 11, 297–298 (2012).PubMedGoogle Scholar
  102. 102.
    Gijselinck, I. et al. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study, Lancet Neurol. 11, 54–65 (2012).PubMedGoogle Scholar
  103. 103.
    Achi, E. Y. & Rudnicki, S. A. ALS and Frontotemporal Dysfunction: A Review. Neurol. Res. Int. 1–9 (2012).Google Scholar
  104. 104.
    Majounie, E. et al. Repeat expansion in C9ORF72 in Alzheimer’s disease, N. Engl. J. Med. 366, 283–284 (2012).PubMedGoogle Scholar
  105. 105.
    Gijselinck, I. et al. Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALS. Neurobiol. Aging 30, 1329–1331 (2009).PubMedGoogle Scholar
  106. 106.
    Borroni, B. et al. Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum. Mutat. 30, 974–983 (2009).Google Scholar
  107. 107.
    Corrado, L. et al. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum. Mut. 30, 688–694 (2009).PubMedGoogle Scholar
  108. 108.
    Kovacs, G. G. et al. TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea. Mov. Disord. 24, 1843–1847 (2009).PubMedGoogle Scholar
  109. 109.
    Benajiba, L. et al. French Clinical and Genetic Research Network on Frontotemporal Lobar Degeneration /Frontotemporal Lobar Degeneration with Motoneuron Diseas, 2009, TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann. Neurol. 65, 470–473.Google Scholar
  110. 110.
    Kirby, J. et al. Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis. Neurogenetics 11, 217–225 (2010).PubMedGoogle Scholar
  111. 111.
    Kabashi, E. et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572–574 (2008).PubMedGoogle Scholar
  112. 112.
    Van Deerlin, V. M. et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol. 7, 409–416 (2008).PubMedGoogle Scholar
  113. 113.
    Del Bo, R. et al. TARDBP (TDP-43) sequence analysis in patients with familial and sporadic ALS: identification of two novel mutations. Eur. J. Neurol. 16, 727–732 (2009).PubMedGoogle Scholar
  114. 114.
    Bäumer, D., Parkinson, N. & Talbot, K. TARDBP in amyotrophic lateral sclerosis: identification of a novel variant but absence of copy number variation. J. Neurol. Neurosurg. Psychiatry 80, 1283–1285 (2009).PubMedGoogle Scholar
  115. 115.
    Sreedharan, J. et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668–1672 (2008).PubMedGoogle Scholar
  116. 116.
    Yokoseki, A. et al. TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann. Neurol. 63, 538–542 (2008).PubMedGoogle Scholar
  117. 117.
    Rutherford, N. J. et al. Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis. PLoS Genet. 4, 1000193 (2008).Google Scholar
  118. 118.
    Kühnlein, P. et al. Two German kindreds with familial amyotrophic lateral sclerosis due to TARDBP mutations. Arch. Neurol. 65, 1185–1189 (2008).PubMedGoogle Scholar
  119. 119.
    Guerreiro, R. J. et al. TDP-43 is not a common cause of sporadic amyotrophic lateral sclerosis. PLoS One 3, 2450 (2009).Google Scholar
  120. 120.
    Daoud, H. et al. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis. J. Med. Genet. 46, 112–114 (2009).PubMedGoogle Scholar
  121. 121.
    Kamada, M. et al. Screening for TARDBP mutations in Japanese familial amyotrophic lateral sclerosis. J. Neurol. Sci. 284, 69–71 (2009).PubMedGoogle Scholar
  122. 122.
    Kwiatkowski, T. J. et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205–1208 (2009).PubMedGoogle Scholar
  123. 123.
    Huey, E. D. et al. FUS and TDP43 genetic variability in FTD and CBS, Neurobiol. Agin. 33, 9–17 (2012).Google Scholar
  124. 124.
    Van Langenhove, T. et al. Genetic contribution of FUS to frontotemporal lobar degeneration. Neurology 74, 366–371 (2010).PubMedGoogle Scholar
  125. 125.
    Vance, C. et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208–1211 (2009).PubMedGoogle Scholar
  126. 126.
    Belzil, V. V. et al. Mutations in FUS cause FALS and SALS in French and French Canadian populations. Neurology 73, 1176–1179 (2009).PubMedGoogle Scholar
  127. 127.
    Ticozzi, N. et al. Analysis of FUS gene mutation in familial amyotrophic lateral sclerosis within an Italian cohort. Neurology 73, 1180–1185 (2009).PubMedGoogle Scholar
  128. 128.
    Corrado, L. et al. Mutations of FUS gene in sporadic amyotrophic lateral sclerosis. J. Med. Genet. 47, 190–194 (2010).PubMedGoogle Scholar
  129. 129.
    Groen, E. J. et al. FUS mutations in familial amyotrophic lateral sclerosis in the Netherlands. Arch. Neurol. 67, 224–230 (2010).PubMedGoogle Scholar
  130. 130.
    DeJesus-Hernandez, M. et al. De novo truncating FUS gene mutation as a cause of sporadic amyotrophic lateral sclerosis. Hum. Mutat. 31, 1377–1389 (2010).Google Scholar
  131. 131.
    Hewitt, C. et al. Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis. Arch. Neurol. 67, 455–461 (2010).PubMedGoogle Scholar
  132. 132.
    Morita, M. et al. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology 66, 839–844 (2006).PubMedGoogle Scholar
  133. 133.
    Weihl, C. C., Pestronk, A. & Kimonis, V. E. Valosincontaining protein disease: inclusion body myopathy with Paget’s disease of the bone and fronto-temporal dementia. Neuromuscul Disord. 19, 308–315 (2009).PubMedGoogle Scholar
  134. 134.
    Cruts, M., Theuns, J. & Van Broeckhoven, C. Locusspecific mutation databases for neurodegenerative brain diseases. Hum Mutat. 33, 1340–1344 (2012).PubMedGoogle Scholar
  135. 135.
    Weihl, C. C. Valosin-containing protein associated frontotemporal lobar degeneration: clinical presentation, pathologic features and pathogenesis. Curr. Alzheimer. Res. 8, 252–260 (2011).PubMedGoogle Scholar
  136. 136.
    Watts, G. D. et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat. Genet. 36, 377–381 (2004).PubMedGoogle Scholar
  137. 137.
    Ju, J. S. & Weihl, C. C. Inclusion body myopathy, Paget’s disease of the bone and fronto-temporal dementia: a disorder of autophagy. Hum. Mol. Genet. 19, 38–45 (2010).Google Scholar
  138. 138.
    Ju, J. S. & Weihl, C. C. p97/VCP at the intersection of the autophagy and the ubiquitin proteasome system. Autophagy 6, 283–285 (2010).PubMedGoogle Scholar
  139. 139.
    Johnson, J. O. et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68, 857–864 (2010).PubMedGoogle Scholar
  140. 140.
    Koppers, M. et al. VCP mutations in familial and sporadic amyotrophic lateral sclerosis. Neurobiol. Aging 33, 837e7–837e13 (2012).Google Scholar
  141. 141.
    Shi, Z. et al. Characterization of the Asian myopathy patients with VCP mutations. Eur. J. of Neurol. 19, 501–509 (2012).Google Scholar
  142. 142.
    Hübbers, C. U. et al. Pathological consequences of VCP mutations on human striated muscle. Brain 130, 381–393 (2007).PubMedGoogle Scholar
  143. 143.
    Watts, G. D. et al. Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Clin. Genet. 72, 420–426 (2007).PubMedGoogle Scholar
  144. 144.
    Kovach, M. J. et al. Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Mol. Genet. Metab. 74, 458–475 (2001).PubMedGoogle Scholar
  145. 145.
    Kimonis, V. E., Fulchiero, E., Vesa, J. & Watts, G. VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. Biochim. Biophys. Acta 1782, 744–748 (2008).PubMedGoogle Scholar
  146. 146.
    Kaleem, M., Zhao, A., Hamsherem, M. & Myers, A. J. Identification of a novel valosin-containing protein polymorphism in late-onset Alzheimer’s disease. Neurodegener. Dis. 4, 376–381 (2007).PubMedGoogle Scholar
  147. 147.
    Stojkovic, T. et al. Clinical outcome in 19 French and Spanish patients with valosin-containing protein myopathy associated with Paget’s disease of bone and frontotemporal dementia. Neuromuscul. Disord. 19, 316–323 (2009).PubMedGoogle Scholar
  148. 148.
    Spina, S., Murrell, J. R., Vidal, R. & Ghetti, B. Neuropathologic and genetic characterization of frontotemporal lobar degeneration with Ubiquitin-and/or Tdp-43-positive inclusions: A large series. Alzheimer’s & Dementia 4Supp 2, 431 (2008).Google Scholar
  149. 149.
    van der Zee, J. et al. Frontotemporal lobar degeneration with ubiquitin-positive inclusions: a molecular genetic update. Neurodegener. Dis. 4, 227–235 (2007).PubMedGoogle Scholar
  150. 150.
    Kumar, K. R. et al. Two Australian families with inclusion-body myopathy, Paget’s disease of bone and frontotemporal dementia: novel clinical and genetic findings. Neuromuscul. Disord. 20, 330–334 (2010).PubMedGoogle Scholar
  151. 151.
    Tresse, E. et al. VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy 6, 217–227 (2010).PubMedGoogle Scholar
  152. 152.
    Cox, L. E. et al. Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PLoS One 5, 9872 (2010).Google Scholar
  153. 153.
    Skibinski, G. et al. Mutations in the endosomal ESC RTIII-complex subunit CHMP2B in frontotemporal dementia. Nat. Genet. 37, 806–808 (2005).PubMedGoogle Scholar
  154. 154.
    van der Zee, J. et al. CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Hum. Mol. Genet. 17, 313–322 (2008).PubMedGoogle Scholar
  155. 155.
    Momeni, P. et al. Genetic variability in CHMP2B and frontotemporal dementia. Neurodegener. Dis. 3, 129–133 (2006).PubMedGoogle Scholar
  156. 156.
    Parkinson, N. et al. MRC Proteomics in ALS Study; FReJA Consortium. ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology 67, 1074–1077 (2006).PubMedGoogle Scholar
  157. 157.
    Gandhi, S. & Wood, N. W. Genome-wide association studies: the key to unlocking neurodegeneration? Nat Neurosci. 13, 789–794 (2010).PubMedGoogle Scholar
  158. 158.
    Seelaar, H. et al. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review J. Neurol. Neurosurg Psychiatry 82, 476–486 (2011).PubMedGoogle Scholar
  159. 159.
    Gellera, C. et al. 2012, Ubiquilin 2 mutations in Italian patients with amyotrophic lateral sclerosis and frontotemporal dementia J. Neurol. Neurosurg. Psychiatry 183–187 (2012).Google Scholar
  160. 160.
    Chen-Plotkin, A. S. et al. TMEM106B, the risk gene for frontotemporal dementia, is regulated by the microRNA-132/212 cluster and affects progranulin pathways. J. Neurosci. 32, 11213–11227 (2012).PubMedGoogle Scholar
  161. 161.
    Seripa, D. et al. TOMM40, APOE, and APOC1 in primary progressive aphasia and frontotemporal dementia, J. Alzheimers Dis. 31, 731–740 (2012).PubMedGoogle Scholar
  162. 162.
    Bernardi, L. et al. Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia. Neurobiol. Aging 30, 1825–1833 (2009).PubMedGoogle Scholar
  163. 163.
    Marcon, G. et al. A novel Italian presenilin 2 gene mutation with prevalent behavioral phenotype. J. Alzheimers Dis. 16, 509–511 (2009).PubMedGoogle Scholar
  164. 164.
    Boxer, A. L. et al. Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J Neurol Neurosurg Psychiatry 82, 196–203 (2011).PubMedGoogle Scholar
  165. 165.
    Morris, H. R. et al. The genetic and pathological classification of familial frontotemporal dementia. Arch. Neurol. 58, 1813–1816 (2001).PubMedGoogle Scholar
  166. 166.
    Cairns, N. J. et al. Consortium for Frontotemporal Lobar Degeneration, Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol. 114, 5–22 (2007).PubMedGoogle Scholar
  167. 167.
    Leyton, C. E. & Hodges, J. R. Frontotemporal dementias: Recent advances and current controversies. Ann. Indian. Acad. Neurol. 13, 74–80 (2010).Google Scholar
  168. 168.
    Bronner, I. F. et al. Comprehensive mRNA expression profiling distinguishes tauopathies and identifies shared molecular pathways. PLoS One 4, e6826 (2009).PubMedGoogle Scholar
  169. 169.
    Jin, S. C. et al. Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer’s disease Ibero-American cohort. Alzheimers. Res. Ther. 4, 34 (2012).PubMedGoogle Scholar
  170. 170.
    Tsuji, S. Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum. Mol. Genet. 19, 65–70 (2010).Google Scholar
  171. 171.
    Pan, X. D. & Chen, X. C. Clinic, neuropathology and molecular genetics of frontotemporal dementia: a mini-review. Transl Neurodegener. 2, 8 (2013).PubMedGoogle Scholar

Copyright information

© Korean Society of Environmental Risk Assessment and Health Science and Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.College of Bionano Technology, Gachon Bionano Research InstituteGachon UniversitySeongnamSouth Korea
  2. 2.Department of NeurologyChung-Ang University College of MedicineSeoulKorea
  3. 3.Department of Neurology, School of MedicineSeoul National University Bundang HospitalSeoulKorea

Personalised recommendations