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Genetic Variation in the Epigenetic Machinery and Mental Health

  • GENETIC DISORDERS (JF CUBELLS AND EB BINDER, SECTION EDITORS)
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Abstract

DNA methylation and chromatin modifications regulate gene expression and contribute to changes in brain transcriptomes underlying neurodevelopmental and psychiatric disorders. Clinical genetics and preclinical animal models highlight the crucial importance of the correct establishment of epigenetic marks during sensitive windows of development for normal brain function. On the same side of the coin, some of the concerned factors also appear engaged in the programming of experience-dependent long-term effects on mental health following exposure to relevant early-life events. Delineating the particular role of genetic variations in these players could provide new insights into the molecular basis of vulnerability and resilience and advance tailored therapies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Murgatroyd C, Spengler D. Epigenetics of early child development. Front Psychiatry. 2011;2:16.

    Article  PubMed  Google Scholar 

  2. ••McGowan PO, Sasaki A, D’Alessio AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12(3):342–8. GR expression was lower in the brains of the suicide victims who suffered childhood abuse, consistent with high levels of methylation on the gene.

    Article  PubMed  CAS  Google Scholar 

  3. Hansen RS, Wijmenga C, Luo P, et al. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1999;96:14412–7.

    Article  PubMed  CAS  Google Scholar 

  4. Klein CJ, Botuyan MV, Wu Y, et al. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet. 2011;43(6):595–600.

    Article  PubMed  CAS  Google Scholar 

  5. •LaPlant Q, Vialou V, Covington 3rd HE, et al. Dnmt3a regulates emotional behaviour and spine plasticity in the nucleus accumbens. Nat Neurosci. 2010;13(9):1137–43. This study evidenced the importance of DNA methylation and DNMT3a in regulating neuronal and behavioral plasticity to emotional stimuli.

    Article  PubMed  CAS  Google Scholar 

  6. Miller CA, Sweatt JD. Covalent modification of DNA regulates memory formation. Neuron. 2007;53(6):857–69.

    Article  PubMed  CAS  Google Scholar 

  7. Hutnick LK, Golshani P, Namihira M, et al. DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation. Hum Mol Genet. 2009;18(15):2875–88.

    Article  PubMed  CAS  Google Scholar 

  8. Kolodkin MH, Auger AP. Sex difference in the expression of DNA methyltransferase3a (DNMT3a) in the rat amygdala during development. J Neuroendocrinol. 2011;23(7):577–83.

    Article  PubMed  CAS  Google Scholar 

  9. Menger Y, Bettscheider M, Murgatroyd C, et al. Sex differences in brain epigenetics. Epigenomics. 2010;2(6):807–21.

    Article  PubMed  CAS  Google Scholar 

  10. Peerbooms OL, van Os J, Drukker M, et al. Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability? Brain Behav Immun. 2011;25(8):1530–43.

    Article  PubMed  CAS  Google Scholar 

  11. Levav-Rabkin T, Blumkin E, Galron D, et al. Sex-dependent behavioral effects of Mthfr deficiency and neonatal GABA potentiation in mice. Behav Brain Res. 2011;216(2):505–13.

    Article  PubMed  CAS  Google Scholar 

  12. Zhou Z, Yuan Q, Mash DC, et al. Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol. Proc Natl Acad Sci U S A. 2011;108(16):6626–31.

    Article  PubMed  CAS  Google Scholar 

  13. ••Ma DK, Jang MH, Guo JU, et al. Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science. 2009;323(5917):1074–7. This study demonstrates that Gadd45b is required for activity-induced DNA demethylation of specific promoters and expression of corresponding genes necessary for adult neurogenesis.

    Article  PubMed  CAS  Google Scholar 

  14. Lasalle JM, Yasui DH. Evolving role of MeCP2 in Rett syndrome and autism. Epigenomics. 2009;1(1):119–30.

    Article  PubMed  CAS  Google Scholar 

  15. Cobb S, Guy J, Bird A. Reversibility of functional deficits in experimental models of Rett syndrome. Biochem Soc Trans. 2010;38(2):498–506.

    Article  PubMed  CAS  Google Scholar 

  16. Lonetti G, Angelucci A, Morando L, et al. Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice. Biol Psychiatry. 2010;67(7):657–65.

    Article  PubMed  Google Scholar 

  17. ••Murgatroyd C, Patchev AV, Wu Y, et al. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat Neurosci. 2009;12(12):1559–66. This study highlights the role of MeCP2 in mediating early-life adversity.

    Article  PubMed  CAS  Google Scholar 

  18. Feng J, Nestler EJ. MeCP2 and drug addiction. Nat Neurosci. 2010;13(9):1039–41.

    Article  PubMed  CAS  Google Scholar 

  19. Petrij F, Giles RH, Dauwerse HG, et al. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature. 1995;376(6538):348–51.

    Article  PubMed  CAS  Google Scholar 

  20. Oliveira AM, Estévez MA, Hawk JD, et al. Subregion-specific p300 conditional knock-out mice exhibit long-term memory impairments. Learn Mem. 2011;18(3):161–9.

    Article  PubMed  Google Scholar 

  21. •Lopez-Atalaya JP, Ciccarelli A, Viosca J, et al. CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement. EMBO J. 2011. doi:10.1038/emboj.2011.299. This study shows that environmental enrichment alters gene expression by modifying the epigenome and identifies CBP as an important mediator.

  22. Hobara T, Uchida S, Otsuki K, et al. Altered gene expression of histone deacetylases in mood disorder patients. J Psychiatr Res. 2010;44:263–70.

    Article  PubMed  Google Scholar 

  23. Gavin DP, Kartan S, Chase K, et al. Histone deacetylase inhibitors and candidate gene expression: an in vivo and in vitro approach to studying chromatin remodeling in a clinical population. J Psychiatr Res. 2009;43:870–6.

    Article  PubMed  Google Scholar 

  24. Iga J, Ueno S, Yamauchi K, et al. Altered HDAC5 and CREB mRNA expressions in the peripheral leukocytes of major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:628–32.

    Article  PubMed  CAS  Google Scholar 

  25. Belzeaux R, Formisano-Tréziny C, Loundou A, et al. Clinical variations modulate patterns of gene expression and define blood biomarkers in major depression. J Psychiatr Res. 2010;44(16):1205–13.

    Article  PubMed  Google Scholar 

  26. Tsankova NM, Berton O, Renthal W, et al. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci. 2006;9:519–25.

    Article  PubMed  CAS  Google Scholar 

  27. Machado-Vieira R, Ibrahim L, Zarate Jr CA. Histone deacetylases and mood disorders: epigenetic programming in gene-environment interactions. CNS Neurosci Ther. 2010. doi:10.1111/j.1755-5949.2010.00203.x.

  28. Kleefstra T, Smidt M, Banning MJ, et al. Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome. J Med Genet. 2005;42(4):299–306.

    Article  PubMed  CAS  Google Scholar 

  29. Balemans MC, Huibers MM, Eikelenboom NW, et al. Reduced exploration, increased anxiety, and altered social behavior: autistic-like features of euchromatin histone methyl transferase 1 heterozygous knockout mice. Behav Brain Res. 2010;208(1):47–55.

    Article  PubMed  CAS  Google Scholar 

  30. •Covington 3rd HE, Maze I, Sun H, et al. A role for repressive histone methylation in cocaine-induced vulnerability to stress. Neuron. 2011;71(4):656–70. Repeated cocaine administration in mice increases the severity of depressive-like responses; G9a mediates these effects through histone methylation.

    Article  PubMed  CAS  Google Scholar 

  31. Poirier R, Jacquot S, Vaillend C, et al. Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior. Behav Genet. 2007;37(1):31–50.

    Article  PubMed  CAS  Google Scholar 

  32. van Bon BW, Koolen DA, Brueton L, et al. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype. Eur J Hum Genet. 2010;18(2):163–70.

    Article  PubMed  Google Scholar 

  33. Juliandi B, Abematsu M, Nakashima K. Chromatin remodeling in neural stem cell differentiation. Curr Opin Neurobiol. 2010;20(4):408–15.

    Article  PubMed  CAS  Google Scholar 

  34. •Koga M, Ishiguro H, Yazaki S, et al. Involvement of SMARCA2/BRM in the SWI/SNF chromatin-remodeling complex in schizophrenia. Hum Mol Genet. 2009;18(13):2483–94. This study supports the role of an SWI/SNF factor as key to a wide range of pathophysiology associated with SZ.

    Article  PubMed  CAS  Google Scholar 

  35. Gibbons RJ, Wada T, Fisher CA, et al. Mutations in the chromatin-associated protein ATRX. Hum Mutat. 2008;29(6):796–802.

    Article  PubMed  CAS  Google Scholar 

  36. Bérubé NG, Mangelsdorf M, Jagla M, et al. The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis. J Clin Invest. 2005;115(2):258–67.

    PubMed  Google Scholar 

  37. Nogami T, Beppu H, Tokoro T, et al. Reduced expression of the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice. Hippocampus. 2011;21(6):678–87.

    Article  PubMed  CAS  Google Scholar 

  38. •Otsuki K, Uchida S, Wakabayashi Y, et al. Aberrant REST-mediated transcriptional regulation in major depressive disorder. J Psychiatr Res. 2010;44(6):378–84. This study links REST-mediated gene regulation to stress vulnerability.

    Article  PubMed  Google Scholar 

  39. Philibert RA. A meta-analysis of the association of the HOPA12bp polymorphism and schizophrenia. Psychiatric Genetics. 2006;16(2):73–6.

    Article  PubMed  Google Scholar 

  40. Hilton E, Johnston J, Whalen S, et al. BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects. Eur J Hum Genet. 2009;17(10):1325–35.

    Article  PubMed  CAS  Google Scholar 

  41. Weaver IC, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004;7(8):847–54.

    Article  PubMed  CAS  Google Scholar 

  42. Zhang TY, Hellstrom IC, Bagot RC, et al. Maternal care and DNA methylation of a glutamic acid decarboxylase 1 promoter in rat hippocampus. J Neurosci. 2010;30(39):13130–7.

    Article  PubMed  CAS  Google Scholar 

  43. Uchida S, Hara K, Kobayashi A, et al. Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events. Neuron. 2011;69(2):359–72.

    Article  PubMed  CAS  Google Scholar 

  44. Spratt EG, Nicholas JS, Brady KT, et al. Enhanced cortisol response to stress in children in autism. J Autism Dev Disord. 2011;41:505–11.

    Article  Google Scholar 

  45. McGowan PO, Suderman M, Sasaki A, et al. Broad epigenetic signature of maternal care in the brain of adult rats. PLoS ONE. 2011;6(2):e14739.

    Article  PubMed  CAS  Google Scholar 

  46. Alarcón JM, Malleret G, Touzani K, et al. Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron. 2004;42(6):947–59.

    Article  PubMed  Google Scholar 

  47. Korzus E, Rosenfeld MG, Mayford M. CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron. 2004;42(6):961–72.

    Article  PubMed  CAS  Google Scholar 

  48. Kubicek S, O’Sullivan RJ, August EM, et al. Reversal of H3K9me2 by a small molecule inhibitor for the G9a histone methyltransferase. Molecular Cell. 2007;25:473–81.

    Article  PubMed  CAS  Google Scholar 

  49. Veldic M, Caruncho HJ, Liu WS, et al. DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc Natl Acad Sci U S A. 2004;101(1):348–53.

    Article  PubMed  CAS  Google Scholar 

  50. Higuchi F, Uchida S, Yamagata H, et al. State-dependent changes in the expression of DNA methyltransferases in mood disorder patients. J Psychiatr Res. 2011;45(10):1295–300.

    Article  PubMed  Google Scholar 

  51. Zhu Q, Wang L, Zhang Y, et al. Increased expression of DNA methyltransferase 1 and 3a in human temporal lobe epilepsy. J Mol Neurosci. 2011. doi:10.1007/s12031-011-9602-7.

  52. Poulter MO, Du L, Weaver IC, et al. GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry. 2008;64(8):645–52.

    Article  PubMed  CAS  Google Scholar 

  53. Zhang C, Fang Y, Xie B, et al. DNA methyltransferase3B gene increases risk of early onset schizophrenia. Neurosci Lett. 2009;462(3):308–11.

    Article  PubMed  CAS  Google Scholar 

  54. Zhubi A, Veldic M, Puri NV, et al. An upregulation of DNA-methyltransferase 1 and 3a expressed in telencephalic GABAergic neurons of schizophrenia patients is also detected in peripheral blood lymphocytes. Schizophr Res. 2009;111(1–3):115–22.

    Article  PubMed  CAS  Google Scholar 

  55. Bönsch D, Lenz B, Fiszer R, et al. Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm. 2006;113(9):1299–304.

    Article  PubMed  Google Scholar 

  56. Haggarty P, Hoad G, Harris SE, et al. Human intelligence and polymorphisms in the DNA methyltransferase genes involved in epigenetic marking. PLoS One. 2010;5(6):e11329.

    Article  PubMed  Google Scholar 

  57. Li H, Yamagata T, Mori M, et al. Mutation analysis of methyl-CpG binding protein family genes in autistic patients. Brain Dev. 2005;27(5):321–5.

    Article  PubMed  CAS  Google Scholar 

  58. Allan AM, Liang X, Luo Y, et al. The loss of methyl-CpG binding protein 1 leads to autism-like behavioral deficits. Hum Mol Genet. 2008;17(13):2047–57.

    Article  PubMed  CAS  Google Scholar 

  59. Hendrich B, Guy J, Ramsahoye B, Wilson VA, Bird A. Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev. 2001;15:710–23.

    Article  PubMed  CAS  Google Scholar 

  60. Cukier HN, Rabionet R, Konidari I, et al. Novel variants identified in methyl-CpG binding domain genes in autistic individuals. Neurogenetics. 2010;11(3):291–303.

    Article  PubMed  CAS  Google Scholar 

  61. Benes FM, Lim B, Subburaju S. Site-specific regulation of cell cycle and DNA repair in post-mitotic GABA cells in schizophrenic versus bipolars. Proc Natl Acad Sci U S A. 2009;106(28):11731–6.

    Article  PubMed  CAS  Google Scholar 

  62. Williams SR, Mullegama SV, Rosenfeld JA, et al. Haploinsufficiency of MBD5associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures. Eur J Hum Genet. 2010;18(4):436–41.

    Article  PubMed  Google Scholar 

  63. Sharma RP, Grayson DR, Gavin DP. Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: analysis of the National Brain Databank microarray collection. Schizophr Res. 2008;98(1–3):111–7.

    Article  PubMed  Google Scholar 

  64. Benes FM, Lim B, Matzilevich D, et al. Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars. Proc Natl Acad Sci U S A. 2007;104(24):10164–9.

    Article  PubMed  CAS  Google Scholar 

  65. Montgomery RL, Hsieh J, Barbosa AC, et al. Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development. Proc Natl Acad Sci U S A. 2009;106(19):7876–81.

    Article  PubMed  CAS  Google Scholar 

  66. Williams SR, Aldred MA, DerKaloustian VM, et al. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am J Hum Genet. 2010;87(2):219–28.

    Article  PubMed  CAS  Google Scholar 

  67. Kim T, Park JK, Kim HJ, et al. Association of histone deacetylase genes with schizophrenia in Korean population. Psychiatry Res. 2010;178(2):266–9.

    Article  PubMed  CAS  Google Scholar 

  68. Renthal W, Maze I, Krishnan V, et al. Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron. 2007;56(3):517–29.

    Article  PubMed  CAS  Google Scholar 

  69. Simon D, Laloo B, Barillot M, et al. A mutation in the 3′-UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia. Hum Mol Genet. 2010;19(10):2015–27.

    Article  PubMed  CAS  Google Scholar 

  70. Haberland M, Mokalled MH, Montgomery RL, et al. Epigenetic control of skull morphogenesis by histone deacetylase 8. Genes Dev. 2009;23(14):1625–30.

    Article  PubMed  CAS  Google Scholar 

  71. Roelfsema JH, White SJ, Ariyürek Y, et al. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005;76:572–80.

    Article  PubMed  CAS  Google Scholar 

  72. Adegbola A, Gao H, Sommer S, et al. A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD). Am J Med Genet A. 2008;146A(4):505–11.

    Article  PubMed  CAS  Google Scholar 

  73. Laumonnier F, Holbert S, Ronce N, et al. Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate. J Med Genet. 2005;42(10):780–6.

    Article  PubMed  CAS  Google Scholar 

  74. Kurotaki N, Imaizumi K, Harada N, et al. Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet. 2002;30(4):365–6.

    Article  PubMed  CAS  Google Scholar 

  75. Akbarian S, Huang HS. Epigenetic regulation in human brain-focus on histone lysine methylation. Biol Psychiatry. 2009;65(3):198–203.

    Article  PubMed  CAS  Google Scholar 

  76. Kim SY, Levenson JM, Korsmeyer S, et al. Developmental regulation of EED complex composition governs a switch in global histone modification in brain. J Biol Chem. 2007;282:9962–72.

    Article  PubMed  CAS  Google Scholar 

  77. Pereira JD, Sansom SN, Smith J, et al. Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex. Proc Natl Acad Sci U S A. 2010;107(36):15957–62.

    Article  PubMed  CAS  Google Scholar 

  78. Schaefer A, Sampath SC, Intrator A, et al. Control of cognition and adaptive behaviour by the GLP/G9a epigenetic suppressor complex. Neuron. 2009;64(5):678–91.

    Article  PubMed  CAS  Google Scholar 

  79. Ng SB, Bigham AW, Buckingham KJ, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet. 2010;42(9):790–3.

    Article  PubMed  CAS  Google Scholar 

  80. Hanauer A, Young ID. Coffin-Lowry syndrome: clinical and molecular features. J Med Genet. 2002;39(10):705–13.

    Article  PubMed  CAS  Google Scholar 

  81. Froyen G, Corbett M, Vandewalle J, et al. Submicroscopic duplications of the hydroxysteroiddehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. Am J Hum Genet. 2008;82(2):432–43.

    Article  PubMed  CAS  Google Scholar 

  82. Zhao X, D’ Arca D, Lim WK, et al. The N-Myc-DLL3 cascade is suppressed by the ubiquitin ligase Huwe1 to inhibit proliferation and promote neurogenesis in the developing brain. Dev Cell. 2009;17(2):210–21.

    Article  PubMed  CAS  Google Scholar 

  83. Nascimento RM, Otto PA, de Brouwer AP, et al. UBE2A, which encodes a ubiquitin conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome. Am J Hum Genet. 2006;79(3):549–55.

    Article  PubMed  CAS  Google Scholar 

  84. Shen Y, Dies KA, Holm IA, et al. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. 2010;125:727–35.

    Article  Google Scholar 

  85. Pharmacogenomics JGene expression in blood is associated with risperidone response in children with autism spectrum disorders.. 2011. doi:10.1038/tpj.2011.23.

  86. Roest HP, Baarends WM, de Wit J, et al. The ubiquitin-conjugating DNA repair enzyme HR6A is a maternal factor essential for early embryonic development in mice. Mol Cell Biol. 2004;24(12):5485–95.

    Article  PubMed  CAS  Google Scholar 

  87. Liu Y, Chen G, Norton N, et al. Whole genome association study in a homogenous population in Shandong peninsula of China reveals JARID2 as a susceptibility gene for schizophrenia. J Biomed Biotechnol. 2009;2009:536918.

    PubMed  Google Scholar 

  88. Boerkoel CF, Takashima H, John J, et al. Mutant chromatin remodeling protein SMARCAL1 causes Schimkeimmuno-osseous dysplasia. Nat Genet. 2002;30(2):215–20.

    Article  PubMed  CAS  Google Scholar 

  89. Vissers LE, van Ravenswaaij CM, Admiraal R, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004;36:955–7.

    Article  PubMed  CAS  Google Scholar 

  90. Layman WS, McEwen DP, Beyer LA, et al. Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Hum Mol Genet. 2009;18(11):1909–23.

    Article  PubMed  CAS  Google Scholar 

  91. Rademacher N, Hambrock M, Fischer U, et al. Identification of a novel CDKL5 exon and pathogenic mutations in patients with severe mental retardation, early-onset seizures and Rett-like features. Neurogenetics. 2011;12(2):165–7.

    Article  PubMed  Google Scholar 

  92. Chen Q, Zhu YC, Yu J, et al. CDKL5, a protein associated with Rett syndrome, regulates neuronal morphogenesis via Rac1 signaling. J Neurosci. 2010;30(38):12777–86.

    Article  PubMed  CAS  Google Scholar 

  93. Yntema HG, van den Helm B, Kissing J, et al. A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation. Genomics. 1999;62(3):332–43.

    Article  PubMed  CAS  Google Scholar 

  94. Ng D, Thakker N, Corcoran CM, et al. Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR. Nat Genet. 2004;36(4):411–6.

    Article  PubMed  CAS  Google Scholar 

  95. Lower KM, Turner G, Kerr BA, et al. Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome. Nat Genet. 2002;32(4):661–5.

    Article  PubMed  CAS  Google Scholar 

  96. Tarpey PS, Smith R, Pleasance E, et al. A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet. 2009;41:535–43.

    Article  PubMed  CAS  Google Scholar 

  97. Willemsen MH, Fernandez BA, Bacino CA, et al. Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome. Eur J Hum Genet. 2010;18(4):429–35.

    Article  PubMed  CAS  Google Scholar 

  98. Nicolas E, Poitelon Y, Chouery E, et al. CAMOS, a nonprogressive, autosomal recessive, congenital cerebellar ataxia, is caused by a mutant zinc-finger protein, ZNF592. Eur J Hum Genet. 2010;18(10):1107–13.

    Article  PubMed  CAS  Google Scholar 

  99. Schwartz CE, Tarpey PS, Lubs HA, et al. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet. 2007;44(7):472–7.

    Article  PubMed  CAS  Google Scholar 

  100. Hashimoto S, Boissel S, Zarhrate M, et al. MED23 mutation links intellectual disability to dysregulation of immediate early gene expression. Science. 2011;333(6046):1161–3.

    Article  PubMed  CAS  Google Scholar 

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    Chris Murgatroyd & Dietmar Spengler

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Murgatroyd, C., Spengler, D. Genetic Variation in the Epigenetic Machinery and Mental Health. Curr Psychiatry Rep 14, 138–149 (2012). https://doi.org/10.1007/s11920-012-0255-1

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