Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS

Neuron

Volumn 72, Issue 2, 2011, Pages 245-256

  DeJesus Hernandez, Mariely ^a   Mackenzie, Ian R ^b   Boeve, Bradley F ^c   Boxer, Adam L ^d   Baker, Matt ^a   Rutherford, Nicola J ^a   Nicholson, Alexandra M ^a   Finch, NiCole A ^a   Flynn, Heather ^c   Adamson, Jennifer ^a   Kouri, Naomi ^a   Wojtas, Aleksandra ^a   Sengdy, Pheth ^b   Hsiung, Ging Yuek R ^b   Karydas, Anna ^d   Seeley, William W ^d   Josephs, Keith A ^c   Coppola, Giovanni ^e   Geschwind, Daniel H ^e   Wszolek, Zbigniew K ^a   Feldman, Howard ^b,f   Knopman, David S ^c   Petersen, Ronald C ^c   Miller, Bruce L ^d   Dickson, Dennis W ^a   Boylan, Kevin B ^a   Graff Radford, Neill R ^a   Rademakers, Rosa ^a   more..

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c MAYO CLINIC ROCHESTER   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TAR DNA BINDING PROTEIN;

ADULT; AGED; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CHROMOSOME 9P; CONTROLLED STUDY; DNA STRUCTURE; FAMILY; FRONTOTEMPORAL DEMENTIA; GENE MUTATION; GENETIC ASSOCIATION; HETEROZYGOTE; HEXANUCLEOTIDE REPEAT; HUMAN; HUMAN CELL; HUMAN TISSUE; MAJOR CLINICAL STUDY; NEUROPATHOLOGY; NUCLEOTIDE SEQUENCE; OPEN READING FRAME; PHENOTYPE; PRIORITY JOURNAL; RNA SPLICING;

ALLELES; AMYOTROPHIC LATERAL SCLEROSIS; CHROMOSOMES, HUMAN, PAIR 9; DNA REPEAT EXPANSION; FEMALE; FRONTOTEMPORAL DEMENTIA; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HAPLOTYPES; HUMANS; MALE; MICROSATELLITE REPEATS; PEDIGREE; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS;

EID: 80054832080     PISSN: 08966273     EISSN: 10974199     Source Type: Journal    
DOI: 10.1016/j.neuron.2011.09.011     Document Type: Article

References (54)

1. Ahmed Z., Sheng H., Xu Y.F., Lin W.L., Innes A.E., Gass J., Yu X., Wuertzer C.A., Hou H., Chiba S., et al. Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful aging. Am. J. Pathol. 2010, 177:311-324.
2. Baker M., Mackenzie I.R., Pickering-Brown S.M., Gass J., Rademakers R., Lindholm C., Snowden J., Adamson J., Sadovnick A.D., Rollinson S., et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006, 442:916-919.
3. Bäumer D., Ansorge O., Almeida M., Talbot K. The role of RNA processing in the pathogenesis of motor neuron degeneration. Expert Rev. Mol. Med. 2010, 12:e21.
4. Boxer A.L., Mackenzie I.R., Boeve B.F., Baker M., Seeley W.W., Crook R., Feldman H., Hsiung G.Y., Rutherford N., Laluz V., et al. Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J. Neurol. Neurosurg. Psychiatry 2011, 82:196-203.
5. Brook J.D., McCurrach M.E., Harley H.G., Buckler A.J., Church D., Aburatani H., Hunter K., Stanton V.P., Thirion J.P., Hudson T., et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell 1992, 68:799-808.
6. Buratti E., Brindisi A., Giombi M., Tisminetzky S., Ayala Y.M., Baralle F.E. TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J. Biol. Chem. 2005, 280:37572-37584.
7. Cartegni L., Wang J., Zhu Z., Zhang M.Q., Krainer A.R. ESEfinder: A web resource to identify exonic splicing enhancers. Nucleic Acids Res. 2003, 31:3568-3571.
8. Cruts M., Gijselinck I., van der Zee J., Engelborghs S., Wils H., Pirici D., Rademakers R., Vandenberghe R., Dermaut B., Martin J.J., et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006, 442:920-924.
9. Daughters R.S., Tuttle D.L., Gao W., Ikeda Y., Moseley M.L., Ebner T.J., Swanson M.S., Ranum L.P. RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet. 2009, 5:e1000600. 10.1371/journal.pgen.1000600.
10. Galloway J.N., Nelson D.L. Evidence for RNA-mediated toxicity in the fragile X-associated tremor/ataxia syndrome. Future Neurol 2009, 4:785.
11. Gijselinck I., Engelborghs S., Maes G., Cuijt I., Peeters K., Mattheijssens M., Joris G., Cras P., Martin J.J., De Deyn P.P., et al. Identification of 2 Loci at chromosomes 9 and 14 in a multiplex family with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Arch. Neurol. 2010, 67:606-616.
12. Giordana M.T., Ferrero P., Grifoni S., Pellerino A., Naldi A., Montuschi A. Dementia and cognitive impairment in amyotrophic lateral sclerosis: a review. Neurol. Sci. 2011, 32:9-16.
13. Graff-Radford N.R., Woodruff B.K. Frontotemporal dementia. Semin. Neurol. 2007, 27:48-57.
14. Gros-Louis F., Gaspar C., Rouleau G.A. Genetics of familial and sporadic amyotrophic lateral sclerosis. Biochim. Biophys. Acta 2006, 1762:956-972.
15. Guo A., Tapia L., Bamji S.X., Cynader M.S., Jia W. Progranulin deficiency leads to enhanced cell vulnerability and TDP-43 translocation in primary neuronal cultures. Brain Res. 2010, 1366:1-8.
16. Hantash F.M., Goos D.G., Tsao D., Quan F., Buller-Burckle A., Peng M., Jarvis M., Sun W., Strom C.M. Qualitative assessment of FMR1 (CGG)n triplet repeat status in normal, intermediate, premutation, full mutation, and mosaic carriers in both sexes: implications for fragile X syndrome carrier and newborn screening. Genet. Med. 2010, 12:162-173.
17. Kabashi E., Valdmanis P.N., Dion P., Spiegelman D., McConkey B.J., Vande Velde C., Bouchard J.P., Lacomblez L., Pochigaeva K., Salachas F., et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 2008, 40:572-574.
18. Kobayashi H., Abe K., Matsuura T., Ikeda Y., Hitomi T., Akechi Y., Habu T., Liu W., Okuda H., Koizumi A. Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am. J. Hum. Genet. 2011, 89:121-130.
19. Kwiatkowski T.J., Bosco D.A., Leclerc A.L., Tamrazian E., Vanderburg C.R., Russ C., Davis A., Gilchrist J., Kasarskis E.J., Munsat T., et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009, 323:1205-1208.
20. Laaksovirta H., Peuralinna T., Schymick J.C., Scholz S.W., Lai S.L., Myllykangas L., Sulkava R., Jansson L., Hernandez D.G., Gibbs J.R., et al. Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study. Lancet Neurol. 2010, 9:978-985.
21. Lagier-Tourenne C., Polymenidou M., Cleveland D.W. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum. Mol. Genet. 2010, 19(R1):R46-R64.
22. Le Ber I., Camuzat A., Berger E., Hannequin D., Laquerrière A., Golfier V., Seilhean D., Viennet G., Couratier P., Verpillat P., et al. Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease. Neurology 2009, 72:1669-1676. French Research Network on FTD/FTD-MND.
23. Liquori C.L., Ricker K., Moseley M.L., Jacobsen J.F., Kress W., Naylor S.L., Day J.W., Ranum L.P. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 2001, 293:864-867.
24. Lomen-Hoerth C., Anderson T., Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 2002, 59:1077-1079.
25. Lomen-Hoerth C., Murphy J., Langmore S., Kramer J.H., Olney R.K., Miller B. Are amyotrophic lateral sclerosis patients cognitively normal?. Neurology 2003, 60:1094-1097.
26. Luty A.A., Kwok J.B., Thompson E.M., Blumbergs P., Brooks W.S., Loy C.T., Dobson-Stone C., Panegyres P.K., Hecker J., Nicholson G.A., et al. Pedigree with frontotemporal lobar degeneration-motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9. BMC Neurol. 2008, 8:32.
27. Mackenzie I.R., Bigio E.H., Ince P.G., Geser F., Neumann M., Cairns N.J., Kwong L.K., Forman M.S., Ravits J., Stewart H., et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann. Neurol. 2007, 61:427-434.
28. Mackenzie I.R., Neumann M., Bigio E.H., Cairns N.J., Alafuzoff I., Kril J., Kovacs G.G., Ghetti B., Halliday G., Holm I.E., et al. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol. 2009, 117:15-18.
29. Mahadevan M., Tsilfidis C., Sabourin L., Shutler G., Amemiya C., Jansen G., Neville C., Narang M., Barceló J., O'Hoy K., et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science 1992, 255:1253-1255.
30. Miller J.W., Urbinati C.R., Teng-Umnuay P., Stenberg M.G., Byrne B.J., Thornton C.A., Swanson M.S. Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J. 2000, 19:4439-4448.
31. Mok K., Traynor B., Schymick J., Tienari P., Laaksovirta H., Peuralinna T., Myllykangas L., Chio A., Shatunov A., Boeve B., et al. The chromosome 9 ALS and FTD locus is probably derived from a single founder. Neurobiol. Aging 2011, in press. Published online September 16, 2011. 10.1016/j.neurobiolaging.2011.08.005.
32. Morita M., Al-Chalabi A., Andersen P.M., Hosler B., Sapp P., Englund E., Mitchell J.E., Habgood J.J., de Belleroche J., Xi J., et al. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology 2006, 66:839-844.
33. Moseley M.L., Zu T., Ikeda Y., Gao W., Mosemiller A.K., Daughters R.S., Chen G., Weatherspoon M.R., Clark H.B., Ebner T.J., et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat. Genet. 2006, 38:758-769.
34. Neary D., Snowden J.S., Gustafson L., Passant U., Stuss D., Black S., Freedman M., Kertesz A., Robert P.H., Albert M., et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998, 51:1546-1554.
35. Neumann M., Sampathu D.M., Kwong L.K., Truax A.C., Micsenyi M.C., Chou T.T., Bruce J., Schuck T., Grossman M., Clark C.M., et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006, 314:130-133.
36. Pearson J.P., Williams N.M., Majounie E., Waite A., Stott J., Newsway V., Murray A., Hernandez D., Guerreiro R., Singleton A.B., et al. Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p. J. Neurol. 2011, 258:647-655.
37. Phukan J., Pender N.P., Hardiman O. Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurol. 2007, 6:994-1003.
38. Renton A.E., Majounie E., Waite A., Simón-Sánchez J., Rollinson S., Gibbs J.R., Schymick J.C., Laaksovirta H., van Swieten J.C., Myllykangas L., et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011, 72. ITALSGEN Consortium, in press. Published online September 21, 2011. 10.1016/j.neuron.2011.09.010.
39. Rosen D.R., Siddique T., Patterson D., Figlewicz D.A., Sapp P., Hentati A., Donaldson D., Goto J., O'Regan J.P., Deng H.X., et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993, 362:59-62.
40. Sato N., Amino T., Kobayashi K., Asakawa S., Ishiguro T., Tsunemi T., Takahashi M., Matsuura T., Flanigan K.M., Iwasaki S., et al. Spinocerebellar ataxia type 31 is associated with " inserted" penta-nucleotide repeats containing (TGGAA)n. Am. J. Hum. Genet. 2009, 85:544-557.
41. Shatunov A., Mok K., Newhouse S., Weale M.E., Smith B., Vance C., Johnson L., Veldink J.H., van Es M.A., van den Berg L.H., et al. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol. 2010, 9:986-994.
42. Smith P.J., Zhang C., Wang J., Chew S.L., Zhang M.Q., Krainer A.R. An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers. Hum. Mol. Genet. 2006, 15:2490-2508.
43. Sofola O.A., Jin P., Qin Y., Duan R., Liu H., de Haro M., Nelson D.L., Botas J. RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. Neuron 2007, 55:565-571.
44. Sreedharan J., Blair I.P., Tripathi V.B., Hu X., Vance C., Rogelj B., Ackerley S., Durnall J.C., Williams K.L., Buratti E., et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008, 319:1668-1672.
45. Tassone F., Iwahashi C., Hagerman P.J. FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor/ataxia syndrome (FXTAS). RNA Biol. 2004, 1:103-105.
46. Timchenko L.T., Miller J.W., Timchenko N.A., DeVore D.R., Datar K.V., Lin L., Roberts R., Caskey C.T., Swanson M.S. Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res. 1996, 24:4407-4414.
47. Todd P.K., Paulson H.L. RNA-mediated neurodegeneration in repeat expansion disorders. Ann. Neurol. 2010, 67:291-300.
48. Valdmanis P.N., Dupre N., Bouchard J.P., Camu W., Salachas F., Meininger V., Strong M., Rouleau G.A. Three families with amyotrophic lateral sclerosis and frontotemporal dementia with evidence of linkage to chromosome 9p. Arch. Neurol. 2007, 64:240-245.
49. Van Deerlin V.M., Sleiman P.M., Martinez-Lage M., Chen-Plotkin A., Wang L.S., Graff-Radford N.R., Dickson D.W., Rademakers R., Boeve B.F., Grossman M., et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat. Genet. 2010, 42:234-239.
50. van Es M.A., Veldink J.H., Saris C.G., Blauw H.M., van Vught P.W., Birve A., Lemmens R., Schelhaas H.J., Groen E.J., Huisman M.H., et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat. Genet. 2009, 41:1083-1087.
51. Vance C., Al-Chalabi A., Ruddy D., Smith B.N., Hu X., Sreedharan J., Siddique T., Schelhaas H.J., Kusters B., Troost D., et al. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain 2006, 129:868-876.
52. Vance C., Rogelj B., Hortobágyi T., De Vos K.J., Nishimura A.L., Sreedharan J., Hu X., Smith B., Ruddy D., Wright P., et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 2009, 323:1208-1211.
53. White M.C., Gao R., Xu W., Mandal S.M., Lim J.G., Hazra T.K., Wakamiya M., Edwards S.F., Raskin S., Teive H.A., et al. Inactivation of hnRNP K by expanded intronic AUUCU repeat induces apoptosis via translocation of PKCdelta to mitochondria in spinocerebellar ataxia 10. PLoS Genet. 2010, 6:e1000984. 10.1371/journal.pgen.1000984.
54. Yin F., Banerjee R., Thomas B., Zhou P., Qian L., Jia T., Ma X., Ma Y., Iadecola C., Beal M.F., et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J. Exp. Med. 2010, 207:117-128.