Skip to main content
Erschienen in: Neurotherapeutics 4/2013

01.10.2013 | Review

Epigenetics, Autism Spectrum, and Neurodevelopmental Disorders

verfasst von: Sampathkumar Rangasamy, Santosh R. D’Mello, Vinodh Narayanan

Erschienen in: Neurotherapeutics | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

Abstract

Epigenetic marks are modifications of DNA and histones. They are considered to be permanent within a single cell during development, and are heritable across cell division. Programming of neurons through epigenetic mechanisms is believed to be critical in neural development. Disruption or alteration in this process causes an array of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Recent studies have provided evidence for an altered epigenetic landscape in ASDs and demonstrated the central role of epigenetic mechanisms in their pathogenesis. Many of the genes linked to the ASDs encode proteins that are involved in transcriptional regulation and chromatin remodeling. In this review we highlight selected neurodevelopmental disorders in which epigenetic dysregulation plays an important role. These include Rett syndrome, fragile X syndrome, Prader–Willi syndrome, Angelman syndrome, and Kabuki syndrome. For each of these disorders, we discuss how advances in our understanding of epigenetic mechanisms may lead to novel therapeutic approaches.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Kanner L. Autistic disturbances of affective contact. Nervous Child 1943;2:217-250. Kanner L. Autistic disturbances of affective contact. Nervous Child 1943;2:217-250.
2.
Zurück zum Zitat Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 2012;30:61:1–19. Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators; Centers for Disease Control and Prevention. Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ 2012;30:61:1–19.
3.
Zurück zum Zitat Brugha TS, McManus S, Bankart J, et al. Epidemiology of autism spectrum disorders in adults in the community in England. Arch Gen Psychiatry 2011;68:459-465.PubMed Brugha TS, McManus S, Bankart J, et al. Epidemiology of autism spectrum disorders in adults in the community in England. Arch Gen Psychiatry 2011;68:459-465.PubMed
4.
Zurück zum Zitat Geschwind DH, Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 2007;17:103-111.PubMed Geschwind DH, Levitt P. Autism spectrum disorders: developmental disconnection syndromes. Curr Opin Neurobiol 2007;17:103-111.PubMed
5.
Zurück zum Zitat Dietert RR, Dietert JM, Dewitt JC. Environmental risk factors for autism. Emerg Health Threats J 2011;4:10.3402. Dietert RR, Dietert JM, Dewitt JC. Environmental risk factors for autism. Emerg Health Threats J 2011;4:10.3402.
6.
Zurück zum Zitat Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations with autism. Science 2007;316:445-449.PubMed Sebat J, Lakshmi B, Malhotra D, et al. Strong association of de novo copy number mutations with autism. Science 2007;316:445-449.PubMed
7.
Zurück zum Zitat Folstein S, Rutter M. Genetic influences and infantile autism. Nature 1977;265:726-728.PubMed Folstein S, Rutter M. Genetic influences and infantile autism. Nature 1977;265:726-728.PubMed
8.
Zurück zum Zitat Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977;18:297-321.PubMed Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977;18:297-321.PubMed
9.
Zurück zum Zitat Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989;30:405-416.PubMed Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989;30:405-416.PubMed
10.
Zurück zum Zitat Wahlström J, Steffenburg S, Hellgren L, Gillberg C. Chromosome findings in twins with early-onset autistic disorder. Am J Med Genet 1989;32:19-21.PubMed Wahlström J, Steffenburg S, Hellgren L, Gillberg C. Chromosome findings in twins with early-onset autistic disorder. Am J Med Genet 1989;32:19-21.PubMed
11.
Zurück zum Zitat Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25:63-77.PubMed Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995;25:63-77.PubMed
12.
Zurück zum Zitat Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011;68:1095-1102.PubMed Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry 2011;68:1095-1102.PubMed
13.
Zurück zum Zitat Waddington CH. The epigenotype. Endeavour 1942;1:18-20. Waddington CH. The epigenotype. Endeavour 1942;1:18-20.
14.
Zurück zum Zitat Fagiolini M, Jensen CL, Champagne FA. Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol 2009;19:207-212.PubMed Fagiolini M, Jensen CL, Champagne FA. Epigenetic influences on brain development and plasticity. Curr Opin Neurobiol 2009;19:207-212.PubMed
15.
Zurück zum Zitat IACC/OARC Autism Spectrum Disorder Research Publications Analysis Report. The Global Landscape of Autism Research. July 2012 Office of Autism Research Coordination (OARC), National Institute of Mental Health and Thomson Reuters, Inc. on behalf of the Interagency Autism Coordinating Committee (IACC). IACC/OARC Autism Spectrum Disorder Research Publications Analysis Report. The Global Landscape of Autism Research. July 2012 Office of Autism Research Coordination (OARC), National Institute of Mental Health and Thomson Reuters, Inc. on behalf of the Interagency Autism Coordinating Committee (IACC).
16.
Zurück zum Zitat Crouse HV. The controlling element in sex chromosome behavior in sciara. Genetics 1960;45:1429-1443.PubMed Crouse HV. The controlling element in sex chromosome behavior in sciara. Genetics 1960;45:1429-1443.PubMed
17.
Zurück zum Zitat Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293:1089-93PubMed Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293:1089-93PubMed
18.
Zurück zum Zitat Sha K. A mechanistic view of genomic imprinting. Annu Rev Genomics Hum Genet 2008;9:197-216.PubMed Sha K. A mechanistic view of genomic imprinting. Annu Rev Genomics Hum Genet 2008;9:197-216.PubMed
19.
Zurück zum Zitat Morey C, Avner P. Genetics and epigenetics of the X chromosome. Ann N Y Acad Sci 2010;1214:E18-E33.PubMed Morey C, Avner P. Genetics and epigenetics of the X chromosome. Ann N Y Acad Sci 2010;1214:E18-E33.PubMed
20.
Zurück zum Zitat Ferguson-Smith AC. Genomic imprinting: the emergence of an epigenetic paradigm. Nat Rev Genet 2011;12:565-575. Ferguson-Smith AC. Genomic imprinting: the emergence of an epigenetic paradigm. Nat Rev Genet 2011;12:565-575.
21.
Zurück zum Zitat Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001;2:21-32.PubMed Reik W, Walter J. Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001;2:21-32.PubMed
22.
Zurück zum Zitat Abramowitz LK, Bartolomei MS. Genomic imprinting: recognition and marking of imprinted loci. Curr Opin Genet Dev 2012;22:72-78.PubMed Abramowitz LK, Bartolomei MS. Genomic imprinting: recognition and marking of imprinted loci. Curr Opin Genet Dev 2012;22:72-78.PubMed
23.
Zurück zum Zitat Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C. High resolution analysis of parent-of-origin allelic expression in the mouse brain. Science. 2010;329:643-648.PubMed Gregg C, Zhang J, Weissbourd B, Luo S, Schroth GP, Haig D, Dulac C. High resolution analysis of parent-of-origin allelic expression in the mouse brain. Science. 2010;329:643-648.PubMed
24.
Zurück zum Zitat Butler MG. Genomic imprinting disorders in humans: a mini-review. J Assist Reprod Genet 2009;26:477-486.PubMed Butler MG. Genomic imprinting disorders in humans: a mini-review. J Assist Reprod Genet 2009;26:477-486.PubMed
25.
Zurück zum Zitat Keverne B. Monoallelic gene expression and mammalian evolution. Bioessays 2009;31:1318-1326.PubMed Keverne B. Monoallelic gene expression and mammalian evolution. Bioessays 2009;31:1318-1326.PubMed
26.
Zurück zum Zitat Tollkuhn J, Xu X, Shah NM. A custody battle for the mind: evidence for extensive imprinting in the brain. Neuron 2010;67:359-362.PubMed Tollkuhn J, Xu X, Shah NM. A custody battle for the mind: evidence for extensive imprinting in the brain. Neuron 2010;67:359-362.PubMed
27.
Zurück zum Zitat Buiting K. Prader–Willi syndrome and Angelman syndrome. Am J Med Genet Part C Semin Med Genet 2010;153C:365-376. Buiting K. Prader–Willi syndrome and Angelman syndrome. Am J Med Genet Part C Semin Med Genet 2010;153C:365-376.
28.
Zurück zum Zitat Nicholls RD, Knepper JL. Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes. Annu Rev Genomics Hum Genet 2001;2:153-175.PubMed Nicholls RD, Knepper JL. Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes. Annu Rev Genomics Hum Genet 2001;2:153-175.PubMed
29.
Zurück zum Zitat Van Buggenhout G, Fryns JP. Angelman syndrome (AS, MIM 105830). Eur J Hum Genet 2009;17:1367-1373.PubMed Van Buggenhout G, Fryns JP. Angelman syndrome (AS, MIM 105830). Eur J Hum Genet 2009;17:1367-1373.PubMed
30.
Zurück zum Zitat Lalande M, Calciano MA. Molecular epigenetics of Angelman syndrome. Cell Mol Life Sci 2007;64:947-960.PubMed Lalande M, Calciano MA. Molecular epigenetics of Angelman syndrome. Cell Mol Life Sci 2007;64:947-960.PubMed
31.
Zurück zum Zitat Mabb AM, Judson MC, Zylka MJ, Philpot BD. Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes. Trends Neurosci 2011;34:293-303.PubMed Mabb AM, Judson MC, Zylka MJ, Philpot BD. Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes. Trends Neurosci 2011;34:293-303.PubMed
32.
Zurück zum Zitat Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 2013;152:1308-1323.PubMed Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 2013;152:1308-1323.PubMed
33.
Zurück zum Zitat Dindot SV, Antalffy BA, Bhattacharjee MB, Beaudet AL. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum Mol Genet 2008;17:111-118.PubMed Dindot SV, Antalffy BA, Bhattacharjee MB, Beaudet AL. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum Mol Genet 2008;17:111-118.PubMed
34.
Zurück zum Zitat Verona RI, Mann MR, Bartolomei MS. Genomic imprinting: intricacies of epigenetic regulation in clusters. Annu Rev Cell Dev Biol 2003;19:237-259.PubMed Verona RI, Mann MR, Bartolomei MS. Genomic imprinting: intricacies of epigenetic regulation in clusters. Annu Rev Cell Dev Biol 2003;19:237-259.PubMed
35.
Zurück zum Zitat Rougeulle C, Cardoso C, Fontés M, Colleaux L, Lalande M. An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript. Nat Genet 1998;19:15-16.PubMed Rougeulle C, Cardoso C, Fontés M, Colleaux L, Lalande M. An imprinted antisense RNA overlaps UBE3A and a second maternally expressed transcript. Nat Genet 1998;19:15-16.PubMed
36.
Zurück zum Zitat Yamasaki K, Joh K, Ohta T, et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum Mol Genet 2003;12:837-847.PubMed Yamasaki K, Joh K, Ohta T, et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum Mol Genet 2003;12:837-847.PubMed
37.
Zurück zum Zitat Chamberlain SJ, Brannan CI. The Prader-Willi syndrome imprinting center activates the paternally expressed murine Ube3a antisense transcript but represses paternal Ube3a. Genomics 2001;73:316-322.PubMed Chamberlain SJ, Brannan CI. The Prader-Willi syndrome imprinting center activates the paternally expressed murine Ube3a antisense transcript but represses paternal Ube3a. Genomics 2001;73:316-322.PubMed
38.
Zurück zum Zitat Meng L, Person RE, Beaudet AL. Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum Mol Genet 2012;21:3001-3012.PubMed Meng L, Person RE, Beaudet AL. Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum Mol Genet 2012;21:3001-3012.PubMed
39.
Zurück zum Zitat Chamberlain SJ, Chen PF, Ng KY, et al. Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes. Proc Natl Acad Sci U S A 2010;107:17668-17673.PubMed Chamberlain SJ, Chen PF, Ng KY, et al. Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes. Proc Natl Acad Sci U S A 2010;107:17668-17673.PubMed
40.
Zurück zum Zitat Huang HS, Allen JA, Mabb AM, et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 2011;481:185-189.PubMed Huang HS, Allen JA, Mabb AM, et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 2011;481:185-189.PubMed
41.
Zurück zum Zitat Lee PD. Disease management of Prader-Willi syndrome. Expert Opin Pharmacother 2002;3:1451-1459.PubMed Lee PD. Disease management of Prader-Willi syndrome. Expert Opin Pharmacother 2002;3:1451-1459.PubMed
42.
Zurück zum Zitat Horsthemke B, Wagstaff J. Mechanisms of imprinting of the Prader-Willi/Angelman region. Am J Med Genet A 2008;146A:2041-2052.PubMed Horsthemke B, Wagstaff J. Mechanisms of imprinting of the Prader-Willi/Angelman region. Am J Med Genet A 2008;146A:2041-2052.PubMed
43.
Zurück zum Zitat Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med 2005;7:1-20.PubMed Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med 2005;7:1-20.PubMed
44.
Zurück zum Zitat Duker AL, Ballif BC, Bawle EV et al. Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. Eur J Hum Genet 2010;18:1196-1201.PubMed Duker AL, Ballif BC, Bawle EV et al. Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader-Willi syndrome. Eur J Hum Genet 2010;18:1196-1201.PubMed
45.
Zurück zum Zitat Berdasco M, Esteller M. Genetic syndromes caused by mutations in epigenetic genes. Hum Genet 2013;132:359-383.PubMed Berdasco M, Esteller M. Genetic syndromes caused by mutations in epigenetic genes. Hum Genet 2013;132:359-383.PubMed
46.
Zurück zum Zitat Schroer RJ, Phelan MC, Michaelis RC, et al. Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 1998;76:327.PubMed Schroer RJ, Phelan MC, Michaelis RC, et al. Autism and maternally derived aberrations of chromosome 15q. Am J Med Genet 1998;76:327.PubMed
47.
Zurück zum Zitat Wang NJ, Liu D, Parokonny AS, Schanen NC. High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage. Am J Hum Genet 2004;75:267-281.PubMed Wang NJ, Liu D, Parokonny AS, Schanen NC. High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage. Am J Hum Genet 2004;75:267-281.PubMed
48.
Zurück zum Zitat Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008;9:341-355.PubMed Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008;9:341-355.PubMed
49.
Zurück zum Zitat Schanen NC. Epigenetics of autism spectrum disorders. Hum Mol Genet 2006;15:R138-R150.PubMed Schanen NC. Epigenetics of autism spectrum disorders. Hum Mol Genet 2006;15:R138-R150.PubMed
50.
Zurück zum Zitat Hogart A, Leung KN, Wang NJ, et al. Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J Med Genet 2009;46:86-93.PubMed Hogart A, Leung KN, Wang NJ, et al. Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J Med Genet 2009;46:86-93.PubMed
51.
Zurück zum Zitat Smith SE, Zhou YD, Zhang G, Jin Z, Stoppel DC, Anderson MP. Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice. Sci Transl Med 2011;3:103ra97PubMed Smith SE, Zhou YD, Zhang G, Jin Z, Stoppel DC, Anderson MP. Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice. Sci Transl Med 2011;3:103ra97PubMed
52.
Zurück zum Zitat Cook EH Jr, Lindgren V, Leventhal BL, et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 1997;60:928-934PubMed Cook EH Jr, Lindgren V, Leventhal BL, et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am J Hum Genet 1997;60:928-934PubMed
53.
Zurück zum Zitat Bolton PF, Dennis NR, Browne CE, et al. The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders. Am J Med Genet 2001;105:675-685PubMed Bolton PF, Dennis NR, Browne CE, et al. The phenotypic manifestations of interstitial duplications of proximal 15q with special reference to the autistic spectrum disorders. Am J Med Genet 2001;105:675-685PubMed
54.
Zurück zum Zitat Di Rocco A, Loggini A, Di Rocco M, et al. Paradoxical worsening of seizure activity with pregabalin in an adult with isodicentric 15 (IDIC-15) syndrome involving duplications of the GABRB3, GABRA5 and GABRG3 genes. BMC Neurol 2013;13:43.PubMed Di Rocco A, Loggini A, Di Rocco M, et al. Paradoxical worsening of seizure activity with pregabalin in an adult with isodicentric 15 (IDIC-15) syndrome involving duplications of the GABRB3, GABRA5 and GABRG3 genes. BMC Neurol 2013;13:43.PubMed
55.
Zurück zum Zitat Hogart A, Nagarajan RP, Patzel KA, Yasui DH, Lasalle JM. 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum Mol Genet 2007;16:691-703.PubMed Hogart A, Nagarajan RP, Patzel KA, Yasui DH, Lasalle JM. 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum Mol Genet 2007;16:691-703.PubMed
56.
Zurück zum Zitat Cummings CJ, Zoghbi HY. Trinucleotide repeats: mechanisms and pathophysiology. Annu Rev Genomics Hum Genet 2000;1:281-328.PubMed Cummings CJ, Zoghbi HY. Trinucleotide repeats: mechanisms and pathophysiology. Annu Rev Genomics Hum Genet 2000;1:281-328.PubMed
57.
Zurück zum Zitat Coffee B, Keith K, Albizua I, et al. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet 2009;85:503-514.PubMed Coffee B, Keith K, Albizua I, et al. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet 2009;85:503-514.PubMed
58.
Zurück zum Zitat Santoro MR, Bray SM, Warren ST. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol 2012;7:219-245.PubMed Santoro MR, Bray SM, Warren ST. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol 2012;7:219-245.PubMed
59.
Zurück zum Zitat Baker JK, Seltzer MM, Greenberg JS. Behaviour problems, maternal internalising symptoms and family relations in families of adolescents and adults with fragile X syndrome. J Intellect Disabil Res 2012;56:984-995.PubMed Baker JK, Seltzer MM, Greenberg JS. Behaviour problems, maternal internalising symptoms and family relations in families of adolescents and adults with fragile X syndrome. J Intellect Disabil Res 2012;56:984-995.PubMed
60.
Zurück zum Zitat Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65:905-914.PubMed Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65:905-914.PubMed
61.
Zurück zum Zitat Bhakar AL, Dölen G, Bear MF. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci 2012;35:417-443.PubMed Bhakar AL, Dölen G, Bear MF. The pathophysiology of fragile X (and what it teaches us about synapses). Annu Rev Neurosci 2012;35:417-443.PubMed
62.
Zurück zum Zitat Heitz D, Rousseau F, Devys D, et al. Isolation of sequences that span the fragile-X and identification of a fragile X-related CpG island. Science 1991;251:1236-1239.PubMed Heitz D, Rousseau F, Devys D, et al. Isolation of sequences that span the fragile-X and identification of a fragile X-related CpG island. Science 1991;251:1236-1239.PubMed
63.
Zurück zum Zitat Hirst MC, White PJ. Cloned human FMR1 trinucleotide repeats exhibit a length-and orientation-dependent instability suggestive of in vivo lagging strand secondary structure. Nucleic Acids Res 1998;26:2353-2358.PubMed Hirst MC, White PJ. Cloned human FMR1 trinucleotide repeats exhibit a length-and orientation-dependent instability suggestive of in vivo lagging strand secondary structure. Nucleic Acids Res 1998;26:2353-2358.PubMed
64.
Zurück zum Zitat Pietrobono R, Tabolacci E, Zalfa F, et al. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 2005;14:267-277.PubMed Pietrobono R, Tabolacci E, Zalfa F, et al. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 2005;14:267-277.PubMed
65.
Zurück zum Zitat Tabolacci E, Pietrobono R, Moscato U, Oostra BA, Chiurazzi P, Neri G. Differential epigenetic modifications in the FMR1 gene of the fragile X syndrome after reactivating pharmacological treatments. Eur J Hum Genet 2005;13:641-648.PubMed Tabolacci E, Pietrobono R, Moscato U, Oostra BA, Chiurazzi P, Neri G. Differential epigenetic modifications in the FMR1 gene of the fragile X syndrome after reactivating pharmacological treatments. Eur J Hum Genet 2005;13:641-648.PubMed
66.
Zurück zum Zitat Sheridan SD, Theriault KM, Reis SA, et al. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One 2011;6:e26203.PubMed Sheridan SD, Theriault KM, Reis SA, et al. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One 2011;6:e26203.PubMed
67.
Zurück zum Zitat Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 2004;291:460-469.PubMed Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 2004;291:460-469.PubMed
68.
Zurück zum Zitat Hagerman RJ, Leavitt BR, Farzin F, et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 2004;74:1051-1056.PubMed Hagerman RJ, Leavitt BR, Farzin F, et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 2004;74:1051-1056.PubMed
69.
Zurück zum Zitat Penagarikano O, Mulle JG, Warren ST. The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet 2007;8:109-129.PubMed Penagarikano O, Mulle JG, Warren ST. The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet 2007;8:109-129.PubMed
70.
Zurück zum Zitat Alisch RS, Wang T, Chopra P, Visootsak J, Conneely KN, Warren ST. Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus. BMC Med Genet 2013;14:18.PubMed Alisch RS, Wang T, Chopra P, Visootsak J, Conneely KN, Warren ST. Genome-wide analysis validates aberrant methylation in fragile X syndrome is specific to the FMR1 locus. BMC Med Genet 2013;14:18.PubMed
71.
Zurück zum Zitat Urbach A, Bar-Nur O, Daley GQ, Benvenisty N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 2010;6:407-411.PubMed Urbach A, Bar-Nur O, Daley GQ, Benvenisty N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 2010;6:407-411.PubMed
72.
Zurück zum Zitat Handa V, Saha T, Usdin K. The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer. Nucleic Acids Res 2003;31:6243-6248.PubMed Handa V, Saha T, Usdin K. The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer. Nucleic Acids Res 2003;31:6243-6248.PubMed
73.
Zurück zum Zitat Verdel A, Jia S, Gerber S, et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 2004;303:672-676.PubMed Verdel A, Jia S, Gerber S, et al. RNAi-mediated targeting of heterochromatin by the RITS complex. Science 2004;303:672-676.PubMed
74.
Zurück zum Zitat Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001;293:1068-1070PubMed Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science 2001;293:1068-1070PubMed
75.
Zurück zum Zitat Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 2008;9:465-476.PubMed Suzuki MM, Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 2008;9:465-476.PubMed
76.
Zurück zum Zitat Hashimshony T, Zhang J, Keshet I, Bustin M, Cedar H. The role of DNA methylation in setting up chromatin structure during development. Nat Genet 2003;34:187-192.PubMed Hashimshony T, Zhang J, Keshet I, Bustin M, Cedar H. The role of DNA methylation in setting up chromatin structure during development. Nat Genet 2003;34:187-192.PubMed
77.
Zurück zum Zitat Lorincz MC, Dickerson DR, Schmitt M, Groudine M. Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat Struct Mol Biol 2004;11:1068-1075.PubMed Lorincz MC, Dickerson DR, Schmitt M, Groudine M. Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat Struct Mol Biol 2004;11:1068-1075.PubMed
78.
Zurück zum Zitat Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 1998;18:6538-6547.PubMed Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 1998;18:6538-6547.PubMed
79.
Zurück zum Zitat Fraga MF, Ballestar E, Montoya G, Taysavang P, Wade PA, Esteller M. The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties. Nucleic Acids Res 2003;31:1765-1774.PubMed Fraga MF, Ballestar E, Montoya G, Taysavang P, Wade PA, Esteller M. The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties. Nucleic Acids Res 2003;31:1765-1774.PubMed
80.
Zurück zum Zitat Rauch C, Trieb M, Wibowo FR, Wellenzohn B, Mayer E, Liedl KR. Towards an understanding of DNA recognition by the methyl-CpG binding domain 1. J Biomol Struct Dyn 2005;22:695-706.PubMed Rauch C, Trieb M, Wibowo FR, Wellenzohn B, Mayer E, Liedl KR. Towards an understanding of DNA recognition by the methyl-CpG binding domain 1. J Biomol Struct Dyn 2005;22:695-706.PubMed
81.
Zurück zum Zitat Hendrich B, Tweedie S. The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet 2003;19:269-277.PubMed Hendrich B, Tweedie S. The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet 2003;19:269-277.PubMed
82.
Zurück zum Zitat Roloff TC, Ropers HH, Nuber UA. Comparative study of methyl-CpG-binding domain proteins. BMC Genomics 2003;4:1.PubMed Roloff TC, Ropers HH, Nuber UA. Comparative study of methyl-CpG-binding domain proteins. BMC Genomics 2003;4:1.PubMed
83.
Zurück zum Zitat Fournier A, Sasai N, Nakao M, Defossez PA. The role of methyl-binding proteins in chromatin organization and epigenome maintenance. Brief Funct Genomics 2012;11:251-264.PubMed Fournier A, Sasai N, Nakao M, Defossez PA. The role of methyl-binding proteins in chromatin organization and epigenome maintenance. Brief Funct Genomics 2012;11:251-264.PubMed
84.
Zurück zum Zitat Wan M, Lee SS, Zhang X, et al. Rett syndrome and beyond:recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 1999;65:1520-1529.PubMed Wan M, Lee SS, Zhang X, et al. Rett syndrome and beyond:recurrent spontaneous and familial MECP2 mutations at CpG hotspots. Am J Hum Genet 1999;65:1520-1529.PubMed
85.
Zurück zum Zitat Moretti P, Zoghbi HY. MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 2006;16:276-281.PubMed Moretti P, Zoghbi HY. MeCP2 dysfunction in Rett syndrome and related disorders. Curr Opin Genet Dev 2006;16:276-281.PubMed
86.
Zurück zum Zitat Gonzales ML, LaSalle JM. The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep 2010;12:127-134.PubMed Gonzales ML, LaSalle JM. The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep 2010;12:127-134.PubMed
87.
Zurück zum Zitat Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999;23:185-188.PubMed Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999;23:185-188.PubMed
88.
Zurück zum Zitat Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol 1983;14:471-479.PubMed Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases. Ann Neurol 1983;14:471-479.PubMed
89.
Zurück zum Zitat Dunn HG. Neurons and neuronal systems involved in the pathophysiologies of Rett syndrome. Brain Dev 2001;23(Suppl. 1):S99-S100.PubMed Dunn HG. Neurons and neuronal systems involved in the pathophysiologies of Rett syndrome. Brain Dev 2001;23(Suppl. 1):S99-S100.PubMed
90.
Zurück zum Zitat Dunn HG, MacLeod PM. Rett syndrome: review of biological abnormalities. Can J Neurol Sci 2001;28:16-29.PubMed Dunn HG, MacLeod PM. Rett syndrome: review of biological abnormalities. Can J Neurol Sci 2001;28:16-29.PubMed
91.
Zurück zum Zitat Bauman ML, Kemper TL, Arin DM. Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome. Neurology 1995;45:1581-1586.PubMed Bauman ML, Kemper TL, Arin DM. Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome. Neurology 1995;45:1581-1586.PubMed
92.
Zurück zum Zitat Bauman ML, Kemper TL, Arin DM. Microscopic observations of the brain in Rett syndrome. Neuropediatrics 1995;26:105-108.PubMed Bauman ML, Kemper TL, Arin DM. Microscopic observations of the brain in Rett syndrome. Neuropediatrics 1995;26:105-108.PubMed
93.
Zurück zum Zitat Belichenko PV, Oldfors A, Hagberg B, Dahlström A. Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents. Neuroreport 1994;5:1509-1513.PubMed Belichenko PV, Oldfors A, Hagberg B, Dahlström A. Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents. Neuroreport 1994;5:1509-1513.PubMed
94.
Zurück zum Zitat Jentarra GM, Olfers SL, Rice SG, et al. Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation. BMC Neurosci 2010;11:19.PubMed Jentarra GM, Olfers SL, Rice SG, et al. Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation. BMC Neurosci 2010;11:19.PubMed
95.
Zurück zum Zitat Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol 2005;20:747-753.PubMed Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol 2005;20:747-753.PubMed
96.
Zurück zum Zitat Guy J, Cheval H, Selfridge J, Bird A. The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 2011;27:631-652.PubMed Guy J, Cheval H, Selfridge J, Bird A. The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 2011;27:631-652.PubMed
97.
Zurück zum Zitat Nan X, Ng HH, Johnson CA, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 1998;393:386-389.PubMed Nan X, Ng HH, Johnson CA, et al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 1998;393:386-389.PubMed
98.
Zurück zum Zitat Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O, Zoghbi HY. An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders. Cell 2013;152:984-996.PubMed Baker SA, Chen L, Wilkins AD, Yu P, Lichtarge O, Zoghbi HY. An AT-hook domain in MeCP2 determines the clinical course of Rett syndrome and related disorders. Cell 2013;152:984-996.PubMed
99.
Zurück zum Zitat Hite KC, Adams VH, Hansen JC. Recent advances in MeCP2 structure and function. Biochem Cell Biol 2009;87:219-227.PubMed Hite KC, Adams VH, Hansen JC. Recent advances in MeCP2 structure and function. Biochem Cell Biol 2009;87:219-227.PubMed
100.
Zurück zum Zitat Van Esch H. MECP2 duplication syndrome. Mol Syndromol 2012;2:128-136.PubMed Van Esch H. MECP2 duplication syndrome. Mol Syndromol 2012;2:128-136.PubMed
101.
Zurück zum Zitat Peters SU, Hundley RJ, Wilson AK, Carvalho CM, Lupski JR, Ramocki MB. Brief report: regression timing and associated features in MECP2 duplication syndrome. J Autism Dev Disord 2013;43:2484-2490.PubMed Peters SU, Hundley RJ, Wilson AK, Carvalho CM, Lupski JR, Ramocki MB. Brief report: regression timing and associated features in MECP2 duplication syndrome. J Autism Dev Disord 2013;43:2484-2490.PubMed
102.
Zurück zum Zitat Ramocki MB, Tavyev YJ, Peters SU. The MECP2 duplication syndrome. Am J Med Genet A 2010;152A:1079-1088.PubMed Ramocki MB, Tavyev YJ, Peters SU. The MECP2 duplication syndrome. Am J Med Genet A 2010;152A:1079-1088.PubMed
103.
Zurück zum Zitat Himada S, Okamoto N, Ito et al. MECP2 duplication syndrome in both genders. Brain Dev 2013;35:411-419. Himada S, Okamoto N, Ito et al. MECP2 duplication syndrome in both genders. Brain Dev 2013;35:411-419.
104.
Zurück zum Zitat Lugtenberg D, Kleefstra T, Oudakker AR, et al. Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum. Genet 2009;17:444-453.PubMed Lugtenberg D, Kleefstra T, Oudakker AR, et al. Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy. Eur J Hum. Genet 2009;17:444-453.PubMed
105.
Zurück zum Zitat Van Esch H, Bauters M, Ignatius J, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 2005;77:442-453.PubMed Van Esch H, Bauters M, Ignatius J, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 2005;77:442-453.PubMed
106.
Zurück zum Zitat Luikenhuis S, Giacometti E, Beard CF, Jaenisch R. Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci U S A 2004;101:6033-6038.PubMed Luikenhuis S, Giacometti E, Beard CF, Jaenisch R. Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci U S A 2004;101:6033-6038.PubMed
107.
Zurück zum Zitat Collins AL, Levenson JM, Vilaythong AP, et al. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 2004;13:2679-2689.PubMed Collins AL, Levenson JM, Vilaythong AP, et al. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 2004;13:2679-2689.PubMed
108.
Zurück zum Zitat Yasui DH, Peddada S, Bieda MC, et al. Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci U S A 2007;104:19416-19421.PubMed Yasui DH, Peddada S, Bieda MC, et al. Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes. Proc Natl Acad Sci U S A 2007;104:19416-19421.PubMed
109.
Zurück zum Zitat Singh J, Saxena A, Christodoulou J, Ravine D. MECP2 genomic structure and function: insights from ENCODE. Nucleic Acids Res 2008;36:6035-6047.PubMed Singh J, Saxena A, Christodoulou J, Ravine D. MECP2 genomic structure and function: insights from ENCODE. Nucleic Acids Res 2008;36:6035-6047.PubMed
110.
Zurück zum Zitat Meehan RR, Lewis JD, Bird AP. Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic Acids Res 1992;20:5085-5092.PubMed Meehan RR, Lewis JD, Bird AP. Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic Acids Res 1992;20:5085-5092.PubMed
111.
Zurück zum Zitat Lewis JD, Meehan RR, Henzel WJ, et al. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 1992;69:905-914.PubMed Lewis JD, Meehan RR, Henzel WJ, et al. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 1992;69:905-914.PubMed
112.
Zurück zum Zitat Jones PL, Veenstra GJ, Wade PA, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 1998;19:187-191.PubMed Jones PL, Veenstra GJ, Wade PA, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 1998;19:187-191.PubMed
113.
Zurück zum Zitat Chahrour M, Jung SY, Shaw C, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008;320:1224-1229.PubMed Chahrour M, Jung SY, Shaw C, et al. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008;320:1224-1229.PubMed
114.
Zurück zum Zitat Mnatzakanian GN, Lohi H, Munteanu I, et al. A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat Genet 2004;36:339-341.PubMed Mnatzakanian GN, Lohi H, Munteanu I, et al. A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome. Nat Genet 2004;36:339-341.PubMed
115.
Zurück zum Zitat Dragich JM, Kim YH, Arnold AP, Schanen NC. Differential distribution of the MeCP2 splice variants in the postnatal mouse brain. J Comp Neurol 2007;501:526-542.PubMed Dragich JM, Kim YH, Arnold AP, Schanen NC. Differential distribution of the MeCP2 splice variants in the postnatal mouse brain. J Comp Neurol 2007;501:526-542.PubMed
116.
Zurück zum Zitat Dastidar SG, Bardai FH, Ma C, et al. Isoform-specific toxicity of Mecp2 in postmitotic neurons: suppression of neurotoxicity by FoxG1. J Neurosci 2012;32:2846-2855.PubMed Dastidar SG, Bardai FH, Ma C, et al. Isoform-specific toxicity of Mecp2 in postmitotic neurons: suppression of neurotoxicity by FoxG1. J Neurosci 2012;32:2846-2855.PubMed
117.
Zurück zum Zitat Zhou Z, Hong EJ, Cohen S, et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent BDNF transcription, dendritic growth, and spine maturation. Neuron 2006;52:255-269.PubMed Zhou Z, Hong EJ, Cohen S, et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent BDNF transcription, dendritic growth, and spine maturation. Neuron 2006;52:255-269.PubMed
118.
Zurück zum Zitat Chen WG, Chang Q, Lin Y, et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 2003;302:885-889.PubMed Chen WG, Chang Q, Lin Y, et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 2003;302:885-889.PubMed
119.
Zurück zum Zitat Zocchi L, Sassone-Corsi P. SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression. Epigenetics 2012;7:695-700.PubMed Zocchi L, Sassone-Corsi P. SIRT1-mediated deacetylation of MeCP2 contributes to BDNF expression. Epigenetics 2012;7:695-700.PubMed
120.
Zurück zum Zitat Horike S, Cai S, Miyano M, Cheng JF, Kohwi-Shigematsu T. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet 2005;37:31-40.PubMed Horike S, Cai S, Miyano M, Cheng JF, Kohwi-Shigematsu T. Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet 2005;37:31-40.PubMed
121.
Zurück zum Zitat Yasui DH, Xu H, Dunaway KW, Lasalle JM, Jin LW, Maezawa I. MeCP2 modulates gene expression pathways in astrocytes. Mol Autism 2013;4:3.PubMed Yasui DH, Xu H, Dunaway KW, Lasalle JM, Jin LW, Maezawa I. MeCP2 modulates gene expression pathways in astrocytes. Mol Autism 2013;4:3.PubMed
122.
Zurück zum Zitat Abuhatzira L, Shamir A, Schones DE, Schäffer AA, Bustin M. The chromatin-binding protein HMGN1 regulates the expression of methyl CpG-binding protein 2 (MECP2) and affects the behavior of mice. J Biol Chem 2011;D286:42051-42062. Abuhatzira L, Shamir A, Schones DE, Schäffer AA, Bustin M. The chromatin-binding protein HMGN1 regulates the expression of methyl CpG-binding protein 2 (MECP2) and affects the behavior of mice. J Biol Chem 2011;D286:42051-42062.
123.
Zurück zum Zitat Mellén M, Ayata P, Dewell S, Kriaucionis S, Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 2012;151:1417-1430.PubMed Mellén M, Ayata P, Dewell S, Kriaucionis S, Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell 2012;151:1417-1430.PubMed
124.
Zurück zum Zitat Nagarajan RP, Patzel KA, Martin M, et al. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Res 2008;1:169-178.PubMed Nagarajan RP, Patzel KA, Martin M, et al. MECP2 promoter methylation and X chromosome inactivation in autism. Autism Res 2008;1:169-178.PubMed
125.
Zurück zum Zitat Nagarajan RP, Hogart AR, Gwye Y, Martin MR, LaSalle JM. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 2006;1:e1-11.PubMed Nagarajan RP, Hogart AR, Gwye Y, Martin MR, LaSalle JM. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 2006;1:e1-11.PubMed
126.
Zurück zum Zitat Grafodatskaya D, Chung B, Szatmari P, Weksberg R. Autism spectrum disorders and epigenetics. J Am Acad Child Adolesc Psychiatry 2010;49:794-809.PubMed Grafodatskaya D, Chung B, Szatmari P, Weksberg R. Autism spectrum disorders and epigenetics. J Am Acad Child Adolesc Psychiatry 2010;49:794-809.PubMed
127.
Zurück zum Zitat 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;17:2047-2057.PubMed 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;17:2047-2057.PubMed
128.
Zurück zum Zitat Cukier HN, Rabionet R, Konidari I, et al. Novel variants identified in methyl-CpG-binding domain genes in autistic individuals. Neurogenetics 2010;11:291-303.PubMed Cukier HN, Rabionet R, Konidari I, et al. Novel variants identified in methyl-CpG-binding domain genes in autistic individuals. Neurogenetics 2010;11:291-303.PubMed
129.
Zurück zum Zitat Cukier HN, Lee JM, Ma D, et al. The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1. Autism Res 2012;5:385-397.PubMed Cukier HN, Lee JM, Ma D, et al. The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1. Autism Res 2012;5:385-397.PubMed
130.
Zurück zum Zitat Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr 1981;99:570-573.PubMed Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr 1981;99:570-573.PubMed
131.
Zurück zum Zitat Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;99:565-569.PubMed Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T. Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 1981;99:565-569.PubMed
132.
Zurück zum Zitat Ng SB, Bigham AW, Buckingham KJ, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 2010;42:790-793.PubMed Ng SB, Bigham AW, Buckingham KJ, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 2010;42:790-793.PubMed
133.
Zurück zum Zitat Bokinni Y. Kabuki syndrome revisited. J Hum Genet 2012;57:223-227.PubMed Bokinni Y. Kabuki syndrome revisited. J Hum Genet 2012;57:223-227.PubMed
134.
Zurück zum Zitat Micale L, Augello B, Fusco C, et al. Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients. Orphanet J Rare Dis 2011;6:38.PubMed Micale L, Augello B, Fusco C, et al. Mutation spectrum of MLL2 in a cohort of Kabuki syndrome patients. Orphanet J Rare Dis 2011;6:38.PubMed
135.
Zurück zum Zitat Priolo M, Micale L, Augello B, et al. Absence of deletion and duplication of MLL2 and KDM6A genes in a large cohort of patients with Kabuki syndrome. Mol Genet Metab 2012;107:627-629.PubMed Priolo M, Micale L, Augello B, et al. Absence of deletion and duplication of MLL2 and KDM6A genes in a large cohort of patients with Kabuki syndrome. Mol Genet Metab 2012;107:627-629.PubMed
136.
Zurück zum Zitat Banka S, Veeramachaneni R, Reardon W, et al. How genetically heterogeneous is Kabuki syndrome: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum. Eur J Hum Genet 2012;20:381-388.PubMed Banka S, Veeramachaneni R, Reardon W, et al. How genetically heterogeneous is Kabuki syndrome: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum. Eur J Hum Genet 2012;20:381-388.PubMed
137.
Zurück zum Zitat Lederer D, Grisart B, Digilio MC, et al. Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. Am J Hum Genet 2012;90:119-124.PubMed Lederer D, Grisart B, Digilio MC, et al. Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome. Am J Hum Genet 2012;90:119-124.PubMed
138.
Zurück zum Zitat Greenfield A, Carrel L, Pennisi D, et al. The UTX gene escapes X inactivation in mice and humans. Hum Mol Genet 1998;7:737-742.PubMed Greenfield A, Carrel L, Pennisi D, et al. The UTX gene escapes X inactivation in mice and humans. Hum Mol Genet 1998;7:737-742.PubMed
139.
Zurück zum Zitat Prasad R, Zhadanov AB, Sedkov Y, et al. Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax. Oncogene 1997;15:549-560.PubMed Prasad R, Zhadanov AB, Sedkov Y, et al. Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax. Oncogene 1997;15:549-560.PubMed
140.
Zurück zum Zitat Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 2008;20:341-348.PubMed Shilatifard A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 2008;20:341-348.PubMed
141.
Zurück zum Zitat Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell 2007;25:1-14.PubMed Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell 2007;25:1-14.PubMed
142.
Zurück zum Zitat Issaeva I, Zonis Y, Rozovskaia T, et al. Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth. Mol Cell Biol 2007;27:1889-1903.PubMed Issaeva I, Zonis Y, Rozovskaia T, et al. Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth. Mol Cell Biol 2007;27:1889-1903.PubMed
143.
Zurück zum Zitat Vicent GP, Nacht AS, Font-Mateu J, et al. Four enzymes cooperate to displace histone H1 during the first minute of hormonal gene activation. Genes Dev 2011;25:845-862.PubMed Vicent GP, Nacht AS, Font-Mateu J, et al. Four enzymes cooperate to displace histone H1 during the first minute of hormonal gene activation. Genes Dev 2011;25:845-862.PubMed
144.
Zurück zum Zitat Guo C, Chang CC, Wortham M, et al. Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways. Proc Natl Acad Sci U S A 2012;109:17603-17608.PubMed Guo C, Chang CC, Wortham M, et al. Global identification of MLL2-targeted loci reveals MLL2's role in diverse signaling pathways. Proc Natl Acad Sci U S A 2012;109:17603-17608.PubMed
145.
Zurück zum Zitat Dhar SS, Lee SH, Kan PY, et al. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. Genes Dev 2012; 26:2749-2762.PubMed Dhar SS, Lee SH, Kan PY, et al. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. Genes Dev 2012; 26:2749-2762.PubMed
146.
Zurück zum Zitat Kerimoglu C, Agis-Balboa RC, Kranz A, et al. Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice. J Neurosci 2013;33:3452-3464.PubMed Kerimoglu C, Agis-Balboa RC, Kranz A, et al. Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice. J Neurosci 2013;33:3452-3464.PubMed
147.
Zurück zum Zitat Saitoh S, Wada T. Parent-of-origin specific histone acetylation and reactivation of a key imprinted gene locus in Prader-Willi syndrome. Am J Hum Genet 2000;66:1958-1962.PubMed Saitoh S, Wada T. Parent-of-origin specific histone acetylation and reactivation of a key imprinted gene locus in Prader-Willi syndrome. Am J Hum Genet 2000;66:1958-1962.PubMed
148.
Zurück zum Zitat Garg SK, Lioy DT, Cheval H, et al. Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome. J Neurosci 2013;33:13612-13620.PubMed Garg SK, Lioy DT, Cheval H, et al. Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome. J Neurosci 2013;33:13612-13620.PubMed
149.
Zurück zum Zitat Derecki NC, Cronk JC, Lu Z, et al. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 2012;484:105-109.PubMed Derecki NC, Cronk JC, Lu Z, et al. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 2012;484:105-109.PubMed
150.
Zurück zum Zitat Martinowich K, Hattori D, Wu H, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 2003;302:890-893PubMed Martinowich K, Hattori D, Wu H, et al. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 2003;302:890-893PubMed
151.
Zurück zum Zitat Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 2006;49:341-348.PubMed Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 2006;49:341-348.PubMed
152.
Zurück zum Zitat Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM. Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 2007;27:10912-10917.PubMed Ogier M, Wang H, Hong E, Wang Q, Greenberg ME, Katz DM. Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J Neurosci 2007;27:10912-10917.PubMed
153.
Zurück zum Zitat Itoh M, Ide S, Takashima S, et al. Methyl CpG-binding protein 2 (a mutation of which causes Rett syndrome) directly regulates insulin-like growth factor binding protein 3 in mouse and human brains. J Neuropathol Exp Neurol 2007;66:117-123.PubMed Itoh M, Ide S, Takashima S, et al. Methyl CpG-binding protein 2 (a mutation of which causes Rett syndrome) directly regulates insulin-like growth factor binding protein 3 in mouse and human brains. J Neuropathol Exp Neurol 2007;66:117-123.PubMed
154.
Zurück zum Zitat Tropea D, Giacometti E, Wilson NR, et al. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A 2009;106:2029-2034.PubMed Tropea D, Giacometti E, Wilson NR, et al. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A 2009;106:2029-2034.PubMed
155.
Zurück zum Zitat Todd PK, Oh SY, Krans A, et al. Histone deacetylases suppress CGG repeat-induced neurodegeneration via transcriptional silencing in models of fragile X tremor ataxia syndrome. PLoS Genet 2010;6:e1001240.PubMed Todd PK, Oh SY, Krans A, et al. Histone deacetylases suppress CGG repeat-induced neurodegeneration via transcriptional silencing in models of fragile X tremor ataxia syndrome. PLoS Genet 2010;6:e1001240.PubMed
156.
Zurück zum Zitat Torrioli M, Vernacotola S, Setini C, et al. Treatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys. Am J Med Genet A 2010;152A:1420-1427.PubMed Torrioli M, Vernacotola S, Setini C, et al. Treatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys. Am J Med Genet A 2010;152A:1420-1427.PubMed
157.
Zurück zum Zitat Jiang J, Jing Y, Cost GJ, et al. Translating dosage compensation to trisomy 21. Nature 2013;500:296-300.PubMed Jiang J, Jing Y, Cost GJ, et al. Translating dosage compensation to trisomy 21. Nature 2013;500:296-300.PubMed
158.
Zurück zum Zitat Gross C, Berry-Kravis EM, Bassell GJ. Therapeutic strategies in fragile X syndrome: dysregulated mGluR signaling and beyond. Neuropsychopharmacology 2012;37:178-195.PubMed Gross C, Berry-Kravis EM, Bassell GJ. Therapeutic strategies in fragile X syndrome: dysregulated mGluR signaling and beyond. Neuropsychopharmacology 2012;37:178-195.PubMed
Metadaten
Titel
Epigenetics, Autism Spectrum, and Neurodevelopmental Disorders
verfasst von
Sampathkumar Rangasamy
Santosh R. D’Mello
Vinodh Narayanan
Publikationsdatum
01.10.2013
Verlag
Springer US
Erschienen in
Neurotherapeutics / Ausgabe 4/2013
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-013-0227-0

Weitere Artikel der Ausgabe 4/2013

Neurotherapeutics 4/2013 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.