Haploinsufficiency of KMT2B, Encoding the Lysine-Specific Histone Methyltransferase 2B, Results in Early-Onset Generalized Dystonia

American Journal of Human Genetics

Volumn 99, Issue 6, 2016, Pages 1377-1387

  Zech, Michael ^a,b   Boesch, Sylvia ^c   Maier, Esther M ^d   Borggraefe, Ingo ^d   Vill, Katharina ^d   Laccone, Franco ^e   Pilshofer, Veronika ^f   Ceballos Baumann, Andres ^b,g   Alhaddad, Bader ^h   Berutti, Riccardo ^a   Poewe, Werner ^c   Haack, Tobias B ^a,h,i   Haslinger, Bernhard ^b   Strom, Tim M ^a,h   Winkelmann, Juliane ^a,b,h,j  

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^d LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^e MEDICAL UNIVERSITY OF VIENNA   (Austria)

^f Krankenhaus der Barmherzigen Schwestern Linz   (Austria)

^g Center for Parkinson's Disease and Movement Disorders Schön Klinik München Schwabing   (Germany)

^h TECHNICAL UNIVERSITY OF MUNICH   (Germany)

ⁱ UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^j NONE   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE METHYLTRANSFERASE; KMT2B PROTEIN; LYSINE SPECIFIC HISTONE METHYLTRANSFERASE 2B; MESSENGER RNA; PROTEIN; UNCLASSIFIED DRUG; HISTONE LYSINE METHYLTRANSFERASE; KMT2B PROTEIN, HUMAN; LYSINE;

ADOLESCENT; ADULT; ARTICLE; AUSTRALIAN; CHILD; CLINICAL ARTICLE; CLINICAL FEATURE; CODON; EXOME; FEMALE; FRAMESHIFT MUTATION; GENE; GENE IDENTIFICATION; GENE SEQUENCE; GENERALIZED DYSTONIA; GENETIC CODE; GERMAN (CITIZEN); HAPLOINSUFFICIENCY; HISTONE MODIFICATION; HUMAN; KMT2B GENE; LOSS OF FUNCTION MUTATION; MALE; NONSENSE MUTATION; PRIORITY JOURNAL; TRANSCRIPTION REGULATION; DYSTONIC DISORDER; GENETICS; METABOLISM; NUCLEOTIDE SEQUENCE; ONSET AGE; PEDIGREE; YOUNG ADULT;

ADOLESCENT; ADULT; AGE OF ONSET; BASE SEQUENCE; CHILD; DYSTONIC DISORDERS; FEMALE; HAPLOINSUFFICIENCY; HISTONE-LYSINE N-METHYLTRANSFERASE; HUMANS; LYSINE; MALE; PEDIGREE; YOUNG ADULT;

EID: 85004144067     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2016.10.010     Document Type: Article

References (43)

1. 1 Albanese, A., Bhatia, K., Bressman, S.B., Delong, M.R., Fahn, S., Fung, V.S., Hallett, M., Jankovic, J., Jinnah, H.A., Klein, C., et al. Phenomenology and classification of dystonia: a consensus update. Mov. Disord. 28 (2013), 863–873.
2. 2 Balint, B., Bhatia, K.P., Dystonia: an update on phenomenology, classification, pathogenesis and treatment. Curr. Opin. Neurol. 27 (2014), 468–476.
3. 3 Klein, C., Genetics in dystonia. Parkinsonism Relat. Disord. 20:Suppl 1 (2014), S137–S142.
4. 4 Domingo, A., Erro, R., Lohmann, K., Novel Dystonia Genes: Clues on Disease Mechanisms and the Complexities of High-Throughput Sequencing. Mov. Disord. 31 (2016), 471–477.
5. 5 Zech, M., Boesch, S., Jochim, A., Weber, S., Meindl, T., Schormair, B., Wieland, T., Lunetta, C., Sansone, V., Messner, M., et al. Clinical exome sequencing in early-onset generalized dystonia and large-scale resequencing follow-up. Mov. Disord., 2016, 10.1002/mds.26808.
6. 6 Lek, M., Karczewski, K.J., Minikel, E.V., Samocha, K.E., Banks, E., Fennell, T., O'Donnell-Luria, A.H., Ware, J.S., Hill, A.J., Cummings, B.B., et al., Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536 (2016), 285–291.
7. 7 Rauch, A., Wieczorek, D., Graf, E., Wieland, T., Endele, S., Schwarzmayr, T., Albrecht, B., Bartholdi, D., Beygo, J., Di Donato, N., et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 380 (2012), 1674–1682.
8. 8 Fromer, M., Pocklington, A.J., Kavanagh, D.H., Williams, H.J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D.M., et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 506 (2014), 179–184.
9. 9 Gulsuner, S., Walsh, T., Watts, A.C., Lee, M.K., Thornton, A.M., Casadei, S., Rippey, C., Shahin, H., Nimgaonkar, V.L., Go, R.C., et al. Consortium on the Genetics of Schizophrenia (COGS), PAARTNERS Study Group. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell 154 (2013), 518–529.
10. 10 Xu, B., Ionita-Laza, I., Roos, J.L., Boone, B., Woodrick, S., Sun, Y., Levy, S., Gogos, J.A., Karayiorgou, M., De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat. Genet. 44 (2012), 1365–1369.
11. 11 Allen, A.S., Berkovic, S.F., Cossette, P., Delanty, N., Dlugos, D., Eichler, E.E., Epstein, M.P., Glauser, T., Goldstein, D.B., Han, Y., et al. Epi4K Consortium, Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature 501 (2013), 217–221.
12. 12 Chesi, A., Staahl, B.T., Jovičić, A., Couthouis, J., Fasolino, M., Raphael, A.R., Yamazaki, T., Elias, L., Polak, M., Kelly, C., et al. Exome sequencing to identify de novo mutations in sporadic ALS trios. Nat. Neurosci. 16 (2013), 851–855.
13. 13 Iossifov, I., O'Roak, B.J., Sanders, S.J., Ronemus, M., Krumm, N., Levy, D., Stessman, H.A., Witherspoon, K.T., Vives, L., Patterson, K.E., et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515 (2014), 216–221.
14. 14 Homsy, J., Zaidi, S., Shen, Y., Ware, J.S., Samocha, K.E., Karczewski, K.J., DePalma, S.R., McKean, D., Wakimoto, H., Gorham, J., et al. De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies. Science 350 (2015), 1262–1266.
15. 15 Samocha, K.E., Robinson, E.B., Sanders, S.J., Stevens, C., Sabo, A., McGrath, L.M., Kosmicki, J.A., Rehnström, K., Mallick, S., Kirby, A., et al. A framework for the interpretation of de novo mutation in human disease. Nat. Genet. 46 (2014), 944–950.
16. 16 Petrovski, S., Wang, Q., Heinzen, E.L., Allen, A.S., Goldstein, D.B., Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet., 9, 2013, e1003709.
17. 17 Kervestin, S., Jacobson, A., NMD: a multifaceted response to premature translational termination. Nat. Rev. Mol. Cell Biol. 13 (2012), 700–712.
18. 18 Dale, R.C., Grattan-Smith, P., Nicholson, M., Peters, G.B., Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single-centre study. Dev. Med. Child Neurol. 54 (2012), 618–623.
19. 19 Gana, S., Veggiotti, P., Sciacca, G., Fedeli, C., Bersano, A., Micieli, G., Maghnie, M., Ciccone, R., Rossi, E., Plunkett, K., et al. 19q13.11 cryptic deletion: description of two new cases and indication for a role of WTIP haploinsufficiency in hypospadias. Eur. J. Hum. Genet. 20 (2012), 852–856.
20. 20 Melo, J.B., Estevinho, A., Saraiva, J., Ramos, L., Carreira, I.M., Cutis Aplasia as a clinical hallmark for the syndrome associated with 19q13.11 deletion: the possible role for UBA2 gene. Mol. Cytogenet., 8, 2015, 21.
21. 21 Forzano, F., Napoli, F., Uliana, V., Malacarne, M., Viaggi, C., Bloise, R., Coviello, D., Di Maria, E., Olivieri, I., Di Iorgi, N., Faravelli, F., 19q13 microdeletion syndrome: Further refining the critical region. Eur. J. Med. Genet. 55 (2012), 429–432.
22. 22 Schuurs-Hoeijmakers, J.H., Vermeer, S., van Bon, B.W., Pfundt, R., Marcelis, C., de Brouwer, A.P., de Leeuw, N., de Vries, B.B., Refining the critical region of the novel 19q13.11 microdeletion syndrome to 750 Kb. J. Med. Genet. 46 (2009), 421–423.
23. 23 Malan, V., Raoul, O., Firth, H.V., Royer, G., Turleau, C., Bernheim, A., Willatt, L., Munnich, A., Vekemans, M., Lyonnet, S., et al. 19q13.11 deletion syndrome: a novel clinically recognisable genetic condition identified by array comparative genomic hybridisation. J. Med. Genet. 46 (2009), 635–640.
24. 24 Kulharya, A.S., Michaelis, R.C., Norris, K.S., Taylor, H.A., Garcia-Heras, J., Constitutional del(19)(q12q13.1) in a three-year-old girl with severe phenotypic abnormalities affecting multiple organ systems. Am. J. Med. Genet. 77 (1998), 391–394.
25. 25 Uhlén, M., Fagerberg, L., Hallström, B.M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., et al. Proteomics. Tissue-based map of the human proteome. Science, 347, 2015, 1260419.
26. 26 Ansari, K.I., Mandal, S.S., Mixed lineage leukemia: roles in gene expression, hormone signaling and mRNA processing. FEBS J. 277 (2010), 1790–1804.
27. 27 Shen, E., Shulha, H., Weng, Z., Akbarian, S., Regulation of histone H3K4 methylation in brain development and disease. Philos. Trans. R. Soc. Lond. B Biol. Sci., 369, 2014, 10.1098/rstb.2013.0514.
28. 28 Vallianatos, C.N., Iwase, S., Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders. Epigenomics 7 (2015), 503–519.
29. 29 Lein, E.S., Hawrylycz, M.J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A.F., Boguski, M.S., Brockway, K.S., Byrnes, E.J., et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445 (2007), 168–176.
30. 30 Glaser, S., Schaft, J., Lubitz, S., Vintersten, K., van der Hoeven, F., Tufteland, K.R., Aasland, R., Anastassiadis, K., Ang, S.L., Stewart, A.F., Multiple epigenetic maintenance factors implicated by the loss of Mll2 in mouse development. Development 133 (2006), 1423–1432.
31. 31 Lubitz, S., Glaser, S., Schaft, J., Stewart, A.F., Anastassiadis, K., Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase Mll2. Mol. Biol. Cell 18 (2007), 2356–2366.
32. 32 Jakovcevski, M., Akbarian, S., Epigenetic mechanisms in neurological disease. Nat. Med. 18 (2012), 1194–1204.
33. 33 Berdasco, M., Esteller, M., Genetic syndromes caused by mutations in epigenetic genes. Hum. Genet. 132 (2013), 359–383.
34. 34 Bai, G., Cheung, I., Shulha, H.P., Coelho, J.E., Li, P., Dong, X., Jakovcevski, M., Wang, Y., Grigorenko, A., Jiang, Y., et al. Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains. Hum. Mol. Genet. 24 (2015), 1441–1456.
35. 35 Takata, A., Xu, B., Ionita-Laza, I., Roos, J.L., Gogos, J.A., Karayiorgou, M., Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene. Neuron 82 (2014), 773–780.
36. 36 Jones, W.D., Dafou, D., McEntagart, M., Woollard, W.J., Elmslie, F.V., Holder-Espinasse, M., Irving, M., Saggar, A.K., Smithson, S., Trembath, R.C., et al. De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am. J. Hum. Genet. 91 (2012), 358–364.
37. 37 Kleefstra, T., Kramer, J.M., Neveling, K., Willemsen, M.H., Koemans, T.S., Vissers, L.E., Wissink-Lindhout, W., Fenckova, M., van den Akker, W.M., Kasri, N.N., et al. Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability. Am. J. Hum. Genet. 91 (2012), 73–82.
38. 38 Ng, S.B., Bigham, A.W., Buckingham, K.J., Hannibal, M.C., McMillin, M.J., Gildersleeve, H.I., Beck, A.E., Tabor, H.K., Cooper, G.M., Mefford, H.C., et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat. Genet. 42 (2010), 790–793.
39. 39 Gupta, S., Kim, S.Y., Artis, S., Molfese, D.L., Schumacher, A., Sweatt, J.D., Paylor, R.E., Lubin, F.D., Histone methylation regulates memory formation. J. Neurosci. 30 (2010), 3589–3599.
40. 40 Lim, D.A., Huang, Y.C., Swigut, T., Mirick, A.L., Garcia-Verdugo, J.M., Wysocka, J., Ernst, P., Alvarez-Buylla, A., Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature 458 (2009), 529–533.
41. 41 Kerimoglu, C., Agis-Balboa, R.C., Kranz, A., Stilling, R., Bahari-Javan, S., Benito-Garagorri, E., Halder, R., Burkhardt, S., Stewart, A.F., Fischer, A., Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice. J. Neurosci. 33 (2013), 3452–3464.
42. 42 Ronan, J.L., Wu, W., Crabtree, G.R., From neural development to cognition: unexpected roles for chromatin. Nat. Rev. Genet. 14 (2013), 347–359.
43. 43 Bjornsson, H.T., Benjamin, J.S., Zhang, L., Weissman, J., Gerber, E.E., Chen, Y.C., Vaurio, R.G., Potter, M.C., Hansen, K.D., Dietz, H.C., Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome. Sci. Transl. Med., 6, 2014, 256ra135.