Whole-genome sequencing reveals a coding non-pathogenic variant tagging a non-coding pathogenic hexanucleotide repeat expansion in C9orf72 as cause of amyotrophic lateral sclerosis

Human Molecular Genetics

Volumn 21, Issue 11, 2012, Pages 2412-2419

  Herdewyn, Sarah ^a,b,c   Zhao, Hui ^a,c   Moisse, Matthieu ^a,c   Race, Valérie ^a   Matthijs, Gert ^a   Reumers, Joke ^a,c   Kusters, Benno ^d   Schelhaas, Helenius J ^d   van den berg, Leonard H ^e   Goris, An ^a,b   Robberecht, Wim ^a,b,c   Lambrechts, Diether ^a,c   Van Damme, Philip ^a,b,c  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b Leuven Institute for Neurodegenerative Disorders (LIND)   (Belgium)

^c DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; DNA; HEXANUCLEOTIDE; NUCLEOTIDE; PROTEIN; PROTEIN SPAG 8; UNCLASSIFIED DRUG;

ADULT; AGED; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; AUTOSOMAL DOMINANT DISORDER; CHROMOSOME 9P; CLINICAL ARTICLE; CONTROLLED STUDY; DYSARTHRIA; DYSPHAGIA; FRONTOTEMPORAL DEMENTIA; GENE LOCUS; GENE MUTATION; GENE SEQUENCE; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HUMAN; MUSCLE WEAKNESS; NUCLEOTIDE REPEAT; PEDIGREE; PRIORITY JOURNAL; TANDEM REPEAT;

ADULT; AGE OF ONSET; AGED; AMYOTROPHIC LATERAL SCLEROSIS; CHROMOSOME MAPPING; DNA REPEAT EXPANSION; FEMALE; GENETIC VARIATION; GENOME, HUMAN; HAPLOTYPES; HUMANS; MALE; MIDDLE AGED; PEDIGREE; PROTEINS;

EID: 84861130735     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/dds055     Document Type: Article

References (43)

1. Rowland, L.P. and Shneider, N.A. (2001) Amyotrophic lateral sclerosis. N. Engl. J. Med., 344, 1688-1700.
2. Phukan, J., Pender, N.P. and Hardiman, O. (2007) Cognitive impairment in amyotrophic lateral sclerosis. Lancet. Neurol., 6, 994-1003.
3. 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. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science, 314, 130-133.
4. Dion, P.A., Daoud, H. and Rouleau, G.A. (2009) Genetics of motor neuron disorders: new insights into pathogenic mechanisms. Nat. Rev. Genet., 10, 769-782.
5. 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. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 362, 59-62.
6. 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. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet., 40, 572-574.
7. 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. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science, 319, 1668-1672.
8. Kwiatkowski, T.J Jr, Bosco, D.A., Leclerc, A.L., Tamrazian, E., Vanderburg, C.R., Russ, C., Davis, A., Gilchrist, J., Kasarskis, E.J., Munsat, T. et al. (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science, 323, 1205-1208.
9. Vance, C., Rogelj, B., Hortobagyi, T., De Vos, K.J., Nishimura, A.L., Sreedharan, J., Hu, X., Smith, B., Ruddy, D., Wright, P. et al. (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science, 323, 1208-1211.
10. Greenway, M.J., Andersen, P.M., Russ, C., Ennis, S., Cashman, S., Donaghy, C., Patterson, V., Swingler, R., Kieran, D., Prehn, J. et al. (2006) ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat. Genet., 38, 411-413.
11. Nishimura, A.L., Mitne-Neto, M., Silva, H.C., Richieri-Costa, A., Middleton, S., Cascio, D., Kok, F., Oliveira, J.R., Gillingwater, T., Webb, J. et al. (2004) A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am. J. Hum. Genet., 75, 822-831.
12. Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H. et al. (2010) Mutations of optineurin in amyotrophic lateral sclerosis. Nature, 465, 223-226.
13. Johnson, J.O., Mandrioli, J., Benatar, M., Abramzon, Y., Van Deerlin, V.M., Trojanowski, J.Q., Gibbs, J.R., Brunetti, M., Gronka, S., Wuu, J. et al. (2010) Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron, 68, 857-864.
14. Hand, C.K., Khoris, J., Salachas, F., Gros-Louis, F., Lopes, A.A., Mayeux-Portas, V., Brewer, C.G., Brown, R.H Jr., Meininger, V., Camu, W. et al. (2002) A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q. Am. J. Hum. Genet., 70, 251-256.
15. Sapp, P.C., Hosler, B.A., McKenna-Yasek, D., Chin, W., Gann, A., Genise, H., Gorenstein, J., Huang, M., Sailer, W., Scheffler, M. et al. (2003) Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis. Am. J. Hum. Genet., 73, 397-403.
16. Hosler, B.A., Siddique, T., Sapp, P.C., Sailor, W., Huang, M.C., Hossain, A., Daube, J.R., Nance, M., Fan, C., Kaplan, J. et al. (2000) Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA, 284, 1664-1669.
17. 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. (2006) A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology, 66, 839-844.
18. Valdmanis, P.N., Dupre, N., Bouchard, J.P., Camu, W., Salachas, F., Meininger, V., Strong, M. and Rouleau, G.A. (2007) Three families with amyotrophic lateral sclerosis and frontotemporal dementia with evidence of linkage to chromosome 9p. Arch. Neurol., 64, 240-245.
19. 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. (2006) Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain, 129, 868-876.
20. 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. (2011) Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J. Neurol. Neurosurg. Psychiatry, 82, 196-203.
21. 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. (2011) Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p. J. Neurol., 258, 647-655.
22. Rollinson, S., Mead, S., Snowden, J., Richardson, A., Rohrer, J., Halliwell, N., Usher, S., Neary, D., Mann, D., Hardy, J. et al. (2011) Frontotemporal lobar degeneration genome wide association study replication confirms a risk locus shared with amyotrophic lateral sclerosis. Neurobiol. Aging, 32, 758 e751-758 e757.
23. Le Ber, I., Camuzat, A., Berger, E., Hannequin, D., Laquerriere, A., Golfier, V., Seilhean, D., Viennet, G., Couratier, P., Verpillat, P. et al. (2009) Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease. Neurology, 72, 1669-1676.
24. 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. (2010) Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet. Neurol., 9, 986-994.
25. 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. (2010) Identification of 2 Loci at chromosomes 9 and 14 in a multiplex family with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Arch. Neurol., 67, 606-616.
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. (2008) Pedigree with frontotemporal lobar degeneration- motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9. BMC Neurol., 8, 32.
27. Lemmens, R., Race, V., Hersmus, N., Matthijs, G., Van Den Bosch, L., Van Damme, P., Dubois, B., Boonen, S., Goris, A. and Robberecht, W. (2009) TDP-43 M311V mutation in familial amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry, 80, 354-355.
28. Van Damme, P., Goris, A., Race, V., Hersmus, N., Dubois, B., Bosch, L.V., Matthijs, G. and Robberecht, W. (2010) The occurrence of mutations in FUS in a Belgian cohort of patients with familial ALS. Eur. J. Neurol., 17, 754-756.
29. Van Damme, P., Veldink, J.H., van Blitterswijk, M., Corveleyn, A., van Vught, P.W., Thijs, V., Dubois, B., Matthijs, G., van den Berg, L.H. and Robberecht, W. (2011) Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2. Neurology, 76, 2066-2072.
30. Reumers, J., De Rijk, P., Zhao, H., Liekens, A., Smeets, D., Cleary, J., Van Loo, P., Van Den Bossche, M., Catthoor, K., Sabbe, B. et al. (2011) Optimized filtering reduces the error rate in detecting genomic variants by short-read sequencing. Nat. Biotechnol., 30, 61-68.
31. DeJesus-Hernandez, M., Mackenzie, I.R., Boeve, B.F., Boxer, A.L., Baker, M., Rutherford, N.J., Nicholson, A.M., Finch, N.A., Flynn, H., Adamson, J. et al. (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron, 72, 245-256.
32. Renton, A.E., Majounie, E., Waite, A., Simon-Sanchez, J., Rollinson, S., Gibbs, J.R., Schymick, J.C., Laaksovirta, H., van Swieten, J.C., Myllykangas, L. et al. (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron, 72, 257-268.
33. Gijselinck, I., Van Langenhove, T., van der Zee, J., Sleegers, K., Philtjens, S., Kleinberger, G., Janssens, J., Bettens, K., Van Cauwenberghe, C., Pereson, S. et al. (2012) 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.
34. Tsuji, S. (2010) Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum. Mol. Genet., 19, R65-R70.
35. Zimprich, A., Benet-Pages, A., Struhal, W., Graf, E., Eck, S.H., Offman, M.N., Haubenberger, D., Spielberger, S., Schulte, E.C., Lichtner, P. et al. (2011) A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am. J. Hum. Genet., 89, 168-175.
36. Vilarino-Guell, C., Wider, C., Ross, O.A., Dachsel, J.C., Kachergus, J.M., Lincoln, S.J., Soto-Ortolaza, A.I., Cobb, S.A., Wilhoite, G.J., Bacon, J.A. et al. (2011) VPS35 mutations in Parkinson disease. Am. J. Hum. Genet., 89, 162-167.
37. Klein, C.J., Botuyan, M.V., Wu, Y., Ward, C.J., Nicholson, G.A., Hammans, S., Hojo, K., Yamanishi, H., Karpf, A.R., Wallace, D.C. et al. (2011) Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat. Genet., 43, 595-600.
38. Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R., Hulkova, H., Jahnova, H., van der Zee, J., Staropoli, J.F. et al. (2011) Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am. J. Hum. Genet., 89, 241-252.
39. Rios, J., Stein, E., Shendure, J., Hobbs, H.H. and Cohen, J.C. (2010) Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia. Hum. Mol. Genet., 19, 4313-4318.
40. Lupski, J.R., Reid, J.G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D.C., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D.A. et al. (2010) Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N. Engl. J. Med., 362, 1181-1191.
41. Brooks, B.R., Miller, R.G., Swash, M. and Munsat, T.L. (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph. Lateral. Scler. Other Motor Neuron Disord., 1, 293-299.
42. Schrooten, M., Smetcoren, C., Robberecht, W. and Van Damme, P. (2011) Benefit of the Awaji diagnostic algorithm for amyotrophic lateral sclerosis: a prospective study. Ann. Neurol., 70, 79-83.
43. Drmanac, R., Sparks, A.B., Callow, M.J., Halpern, A.L., Burns, N.L., Kermani, B.G., Carnevali, P., Nazarenko, I., Nilsen, G.B., Yeung, G. et al. (2010) Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science, 327, 78-81.