Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia

Nature Genetics

Volumn 49, Issue 2, 2017, Pages 223-237

  Meyer, Esther ^a   Carss, Keren J ^b,c   Rankin, Julia ^d   Nichols, John M E ^e   Grozeva, Detelina ^f   Joseph, Agnel P ^g   Mencacci, Niccolo E ^h   Papandreou, Apostolos ^a,i   Ng, Joanne ^a,i   Barral, Serena ^a   Ngoh, Adeline ^a,i   Ben Pazi, Hilla ^j   Willemsen, Michel A ^k   Arkadir, David ^l   Barnicoat, Angela ⁱ   Bergman, Hagai ^l   Bhate, Sanjay ⁱ   Boys, Amber ^m   Darin, Niklas ⁿ   Foulds, Nicola ^o   Gutowski, Nicholas ^d   Hills, Alison ^p   Houlden, Henry ^h   Hurst, Jane A ⁱ   Israel, Zvi ^q   Kaminska, Margaret ^r   Limousin, Patricia ^s   Lumsden, Daniel ^r   McKee, Shane ^t   Misra, Shibalik ^u   Mohammed, Shekeeb S ^u   Nakou, Vasiliki ^r   Nicolai, Joost ^v   Nilsson, Magnus ^w   Pall, Hardev ^x   Peall, Kathryn J ^y   Peters, Gregory B ^z   Prabhakar, Prab ⁱ   Reuter, Miriam S ^aa   Rump, Patrick ^ab   Segel, Reeval ^l   Sinnema, Margje ^ac   Smith, Martin ^ad   Turnpenny, Peter ^d   White, Susan M ^m,ae   Wieczorek, Dagmar ^af,ag   Wiethoff, Sarah ^h   Wilson, Brian T ⁱ   Winter, Gidon ^j   Wragg, Christopher ^p   Pope, Simon ^s   Heales, Simon J H ^i,s   Morrogh, Deborah ⁱ   Pittman, Alan ^h   Carr, Lucinda J ⁱ   Perez Duenãs, Belen ^ah,ai   Lin, Jean Pierre ^r   Reis, Andre ^aa   Gahl, William A ^aj   Toro, Camilo ^aj   Bhatia, Kailash P ^s   Wood, Nicholas W ^h   Kamsteeg, Erik Jan ^k   Chong, Wui K ⁱ   Gissen, Paul ^e   Topf, Maya ^g   Dale, Russell C ^u   Chubb, Jonathan R ^e   Raymond, F Lucy ^c,f   Kurian, Manju A ^a,i   more..

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^d ROYAL DEVON AND EXETER NHS FOUNDATION TRUST   (United Kingdom)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^g UNIVERSITY OF LONDON   (United Kingdom)

^h UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁱ GREAT ORMOND STREET HOSPITAL   (United Kingdom)

^j SHAARE ZEDEK MEDICAL CENTER   (Israel)

^k RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^l HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^m MURDOCH CHILDREN'S RESEARCH INSTITUTE   (Australia)

ⁿ SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^o SOUTHAMPTON GENERAL HOSPITAL   (United Kingdom)

^p SOUTHMEAD HOSPITAL   (United Kingdom)

^q HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^r EVELINA LONDON CHILDREN S HOSPITAL   (United Kingdom)

^s NATIONAL HOSPITAL FOR NEUROLOGY AND NEUROSURGERY   (United Kingdom)

^t BELFAST CITY HOSPITAL   (United Kingdom)

^u UNIVERSITY OF SYDNEY   (Australia)

^v MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^w UMEÅ UNIVERSITY HOSPITAL   (Sweden)

^x UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^y CARDIFF UNIVERSITY   (United Kingdom)

^z CHILDREN S HOSPITAL AT WESTMEAD   (Australia)

^aa UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^ab UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^ac MAASTRICHT UNIVERSITY   (Netherlands)

^ad JOHN RADCLIFFE HOSPITAL   (United Kingdom)

^ae UNIVERSITY OF MELBOURNE   (Australia)

^af UNIVERSITY OF DUISBURG ESSEN   (Germany)

^ag HEINRICH HEINE UNIVERSITY   (Germany)

^ah UNIVERSITY OF BARCELONA   (Spain)

^ai INSTITUTO DE SALUD CARLOS III   (Spain)

^aj NATIONAL INSTITUTES OF HEALTH   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ACETAZOLAMIDE; DOPAMINE 2 RECEPTOR; HISTONE H3; HISTONE METHYLTRANSFERASE; LEVODOPA; MESSENGER RNA; METHYLPHENIDATE; MIXED LINEAGE LEUKEMIA PROTEIN 4; OXAZEPAM; RISPERIDONE; TYROSINE 3 MONOOXYGENASE; UNCLASSIFIED DRUG; DNA BINDING PROTEIN; HISTONE; HISTONE LYSINE METHYLTRANSFERASE; KMT2B PROTEIN, HUMAN; LYSINE; NUCLEAR PROTEIN;

ADOLESCENT; ADULT; ARTICLE; BRAIN DEPTH STIMULATION; CERVICAL DYSTONIA; CHILD; CHROMOSOME DELETION; CLINICAL ARTICLE; CRANIAL DYSTONIA; DYSTONIA; FACIES; GENE EXPRESSION; GENE MUTATION; GENERALIZED DYSTONIA; HUMAN; MICROCEPHALY; MIDDLE AGED; MOBILIZATION; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN STRUCTURE; SANGER SEQUENCING; SCHOOL CHILD; SEIZURE; SPASMODIC DYSPHONIA; SPASTICITY; VOLUNTARY MOVEMENT; YOUNG ADULT; FEMALE; GENETICS; MALE; METHYLATION; MUTATION;

ADOLESCENT; DNA-BINDING PROTEINS; DYSTONIA; FEMALE; HISTONE-LYSINE N-METHYLTRANSFERASE; HISTONES; HUMANS; LYSINE; MALE; METHYLATION; MUTATION; NUCLEAR PROTEINS;

EID: 85006511643     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.3740     Document Type: Article

References (76)

1. Charlesworth, G., Bhatia, K.P., Wood, N.W. The genetics of dystonia: new twists in an old tale. Brain 136, 2017-2037 (2013).
2. Albanese, A. , et al. Phenomenology and classification of dystonia: a consensus update. Mov. Disord. 28, 863-873 (2013).
3. Ng, J., Papandreou, A., Heales, S.J., Kurian, M.A. Monoamine neurotransmitter disorders-clinical advances and future perspectives. Nat. Rev. Neurol. 11, 567-584 (2015).
4. Shanker, V., Bressman, S.B. Diagnosis and management of dystonia. Continuum (Minneap. Minn.) 22 4 Movement Disorders 1227-1245 (2016).
5. Balint, B., Bhatia, K.P. Isolated and combined dystonia syndromes-an update on new genes and their phenotypes. Eur. J. Neurol. 22, 610-617 (2015).
6. Lin, J.P., Lumsden, D.E., Gimeno, H., Kaminska, M. The impact and prognosis for dystonia in childhood including dystonic cerebral palsy: a clinical and demographic tertiary cohort study. J. Neurol. Neurosurg. Psychiatry 85, 1239-1244 (2014).
7. 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, 618-623 (2012).
8. Lek, M. , et al. Analysis of protein-coding genetic variation in 60, 706 humans. Nature 536, 285-291 (2016).
9. Kircher, M. , et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310-315 (2014).
10. Laimer, J., Hofer, H., Fritz, M., Wegenkittl, S., Lackner, P. MAESTRO-multi agent stability prediction upon point mutations. BMC Bioinformatics 16, 116 (2015).
11. Pires, D.E., Ascher, D.B., Blundell, T.L. DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach. Nucleic Acids Res. 42, W314-W319 (2014).
12. Liu, Z. , et al. Structural and functional insights into the human Börjeson-Forssman-Lehmann syndrome-associated protein PHF6. J. Biol. Chem. 289, 10069-10083 (2014).
13. Musselman, C.A., Kutateladze, T.G. Handpicking epigenetic marks with PHD fingers. Nucleic Acids Res. 39, 9061-9071 (2011).
14. Sanchez, R., Zhou, M.M. The PHD finger: a versatile epigenome reader. Trends Biochem. Sci. 36, 364-372 (2011).
15. Hsieh, J.J., Ernst, P., Erdjument-Bromage, H., Tempst, P., Korsmeyer, S.J. Proteolytic cleavage of MLL generates a complex of N-and C-terminal fragments that confers protein stability and subnuclear localization. Mol. Cell. Biol. 23, 186-194 (2003).
16. Pless, B. , et al. The heterodimerization domains of MLL-FYRN and FYRC-are potential target structures in t(4;11) leukemia. Leukemia 25, 663-670 (2011).
17. Wysocka, J. , et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 121, 859-872 (2005).
18. Song, J.J., Kingston, R.E. WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone H3-binding pocket. J. Biol. Chem. 283, 35258-35264 (2008).
19. Chubb, J.R. , et al. Developmental timing in Dictyostelium is regulated by the Set1 histone methyltransferase. Dev. Biol. 292, 519-532 (2006).
20. Malan, V. , et al. 19q13.11 deletion syndrome: a novel clinically recognisable genetic condition identified by array comparative genomic hybridisation. J. Med. Genet. 46, 635-640 (2009).
21. Kruer, M.C. , et al. Neuroimaging features of neurodegeneration with brain iron accumulation. AJNR Am. J. Neuroradiol. 33, 407-414 (2012).
22. Meyer, E., Kurian, M.A., Hayflick, S.J. Neurodegeneration with brain iron accumulation: genetic diversity and pathophysiological Mechanisms. Annu. Rev. Genomics Hum. Genet. 16, 257-279 (2015).
23. Ozelius, L., Lubarr, N. DYT1 early-onset Isolated dystonia. GeneReviews https://www.ncbi.nlm.nih.gov/books/NBK1492/(1999).
24. Marras, K.C., Münchau, A. Dystonia overview. GeneReviews https://www.ncbi.nlm.nih.gov/books/NBK1155/(2003).
25. Kouzarides, T. Chromatin modifications and their function. Cell 128, 693-705 (2007).
26. Black, J.C., Van Rechem, C., Whetstine, J.R. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol. Cell 48, 491-507 (2012).
27. Creyghton, M.P. , et al. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. USA 107, 21931-21936 (2010).
28. Wang, Y., Li, X., Hu, H. H3K4me2 reliably defines transcription factor binding regions in different cells. Genomics 103, 222-228 (2014).
29. Shao, G.B. , et al. Dynamic patterns of histone H3 lysine 4 methyltransferases and demethylases during mouse preimplantation development. In Vitro Cell. Dev. Biol. Anim. 50, 603-613 (2014).
30. Shen, E., Shulha, H., Weng, Z., Akbarian, S. Regulation of histone H3K4 methylation in brain development and disease. Phil. Trans. R. Soc. Lond. B 369, 20130514 (2014).
31. Jones, W.D. , et al. De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am. J. Hum. Genet. 91, 358-364 (2012).
32. Kleefstra, T. , et al. Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability. Am. J. Hum. Genet. 91, 73-82 (2012).
33. Ng, S.B. , et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat. Genet. 42, 790-793 (2010).
34. Singh, T. , et al. Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nat. Neurosci. 19, 571-577 (2016).
35. Micale, L. , et al. Molecular analysis, pathogenic mechanisms, and readthrough therapy on a large cohort of Kabuki syndrome patients. Hum. Mutat. 35, 841-850 (2014).
36. Ang, S.Y. , et al. KMT2D regulates specific programs in heart development via histone H3 lysine 4 di-methylation. Development 143, 810-821 (2016).
37. Jakovcevski, M. , et al. Neuronal Kmt2a/Mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory. J. Neurosci. 35, 5097-5108 (2015).
38. Benayoun, B.A. , et al. H3K4me3 breadth is linked to cell identity and transcriptional consistency. Cell 158, 673-688 (2014).
39. Muramoto, T., Müller, I., Thomas, G., Melvin, A., Chubb, J.R. Methylation of H3K4 is required for inheritance of active transcriptional states. Curr. Biol. 20, 397-406 (2010).
40. Trabzuni, D. , et al. Quality control parameters on a large dataset of regionally dissected human control brains for whole genome expression studies. J. Neurochem. 119, 275-282 (2011).
41. 1000 Genomes Project Consortium. An integrated map of genetic variation from 1, 092 human genomes. Nature 491, 56-65 (2012).
42. UK10K Consortium. The UK10K project identifies rare variants in health and disease. Nature 526, 82-90 (2015).
43. Raczy, C. , et al. Isaac: ultra-fast whole-genome secondary analysis on Illumina sequencing platforms. Bioinformatics 29, 2041-2043 (2013).
44. Li, H., Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009).
45. Li, H. , et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics25, 2078-2079 (2009).
46. McKenna, A. , et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297-1303 (2010).
47. Danecek, P. , et al. The variant call format and VCFtools. Bioinformatics 27, 2156-2158 (2011).
48. McLaren, W. , et al. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 26, 2069-2070 (2010).
49. Gahl, W.A. , et al. The National Institutes of Health Undiagnosed Diseases Program: insights into rare diseases. Genet. Med. 14, 51-59 (2012).
50. Adams, D.R. , et al. Analysis of DNA sequence variants detected by high-throughput sequencing. Hum. Mutat. 33, 599-608 (2012).
51. Bone, W.P. , et al. Computational evaluation of exome sequence data using human and model organism phenotypes improves diagnostic efficiency. Genet. Med. 18, 608-617 (2016).
52. de Ligt, J. , et al. Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. 367, 1921-1929 (2012).
53. Wang, K., Li, M., Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).
54. Akawi, N. , et al. Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4, 125 families. Nat. Genet.47, 1363-1369 (2015).
55. Deciphering Developmental Disorders Study. Large-scale discovery of novel genetic causes of developmental disorders. Nature 519, 223-228 (2015).
56. Untergasser, A. , et al. Primer3-new capabilities and interfaces. Nucleic Acids Res.40, e115 (2012).
57. Koressaar, T., Remm, M. Enhancements and modifications of primer design program Primer3. Bioinformatics 23, 1289-1291 (2007).
58. Samocha, K.E. , et al. A framework for the interpretation of de novo mutation in human disease. Nat. Genet. 46, 944-950 (2014).
59. Hyland, K. , et al. Cerebrospinal fluid concentrations of pterins and metabolites of serotonin and dopamine in a pediatric reference population. Pediatr. Res. 34, 10-14 (1993).
60. Ormazabal, A. , et al. HPLC with electrochemical and fluorescence detection procedures for the diagnosis of inborn errors of biogenic amines and pterins. J. Neurosci. Methods 142, 153-158 (2005).
61. Finn, R.D. , et al. The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 44, D1, D279-D285 (2016).
62. Landau, M. , et al. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 33, W299-W302 (2005).
63. Söding, J., Biegert, A., Lupas, A.N. The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res. 33, W244-W248 (2005).
64. Sali, A., Blundell, T.L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815 (1993).
65. Shen, M.Y., Sali, A. Statistical potential for assessment and prediction of protein structures. Protein Sci. 15, 2507-2524 (2006).
66. Pettersen, E.F. , et al. UCSF Chimera-A visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612 (2004).
67. Shechter, D., Dormann, H.L., Allis, C.D., Hake, S.B. Extraction, purification and analysis of histones. Nat. Protoc. 2, 1445-1457 (2007).
68. Fey, P., Kowal, A.S., Gaudet, P., Pilcher, K.E., Chisholm, R.L. Protocols for growth and development of Dictyostelium discoideum. Nat. Protoc. 2, 1307-1316 (2007).
69. Fey, P., Dodson, R.J., Basu, S., Chisholm, R.L. One stop shop for everything Dictyostelium: dictyBase and the Dicty Stock Center in 2012. Methods Mol. Biol.983, 59-92 (2013).
70. Faix, J., Gerisch, G., Noegel, A.A. Overexpression of the csA cell adhesion molecule under its own cAMP-regulated promoter impairs morphogenesis in Dictyostelium. J. Cell Sci. 102, 203-214 (1992).
71. Fusaki, N., Ban, H., Nishiyama, A., Saeki, K., Hasegawa, M. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 85, 348-362 (2009).
72. Hartfield, E.M. , et al. Physiological characterisation of human iPS-derived dopaminergic neurons. PLoS One 9, e87388 (2014).
73. Kirkeby, A. , et al. Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. Cell Rep. 1, 703-714 (2012).
74. Frost, J.M. , et al. Evaluation of allelic expression of imprinted genes in adult human blood. PLoS One 5, e13556 (2010).
75. Livak, K.J., Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2CT method. Methods 25, 402-408 (2001).
76. Schindelin, J. , et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676-682 (2012).