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The phenotypic consequences of MECP2 mutations extend beyond Rett syndrome
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4
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0035013739
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MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin
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Trappe R, Laccone F, Cobilanschi J, et al.: MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am J Hum Genet 2001, 68:1093-1101.
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5
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpGbinding protein 2
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Amir RE, Van den Veyver IB, Wan M, et al.: Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpGbinding protein 2. Nat Genet 1999, 23:185-188.
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Amir, R.E.1
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6
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CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders
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Lin C, Franco B, Rosner MR: CDKL5/Stk9 kinase inactivation is associated with neuronal developmental disorders. Hum Mol Genet 2005, 14:3775-3786.
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7
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46149122036
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FOXG1 is responsible for the congenital variant of Rett syndrome
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Investigating patients with a congenital variant of RTT that show evidence of hypotonia and developmental delay from birth, the investigators found novel mutations in the autosomal gene FOXG1, encoding a transcription factor with expression restricted to fetal and adult brain and testes. MeCP2 and FOXG1 might share common molecular mechanisms because of their similar expression patterns and nuclear localization
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Ariani F, Hayek G, Rondinella D, et al.: FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet 2008, 83:89-93. Investigating patients with a congenital variant of RTT that show evidence of hypotonia and developmental delay from birth, the investigators found novel mutations in the autosomal gene FOXG1, encoding a transcription factor with expression restricted to fetal and adult brain and testes. MeCP2 and FOXG1 might share common molecular mechanisms because of their similar expression patterns and nuclear localization.
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Am J Hum Genet
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Ariani, F.1
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Villard L, Kpebe A, Cardoso C, et al.: Two affected boys in a Rett syndrome family: clinical and molecular findings. Neurology 2000, 55:1188-1193.
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Villard, L.1
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10
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3042775154
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Xchromosome inactivation ratios affect wild-type MeCP2 expression within mosaic Rett syndrome and Mecp2-/+ mouse brain
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Braunschweig D, Simcox T, Samaco RC, LaSalle JM: Xchromosome inactivation ratios affect wild-type MeCP2 expression within mosaic Rett syndrome and Mecp2-/+ mouse brain. Hum Mol Genet 2004, 13:1275-1286.
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11
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X-chromosome inactivation patterns are unbalanced and affect the phenotypic outcome in a mouse model of Rett syndrome
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Young JI, Zoghbi HY: X-chromosome inactivation patterns are unbalanced and affect the phenotypic outcome in a mouse model of Rett syndrome. Am J Hum Genet 2004, 74:511-520.
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Am J Hum Genet
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0037158475
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Balanced X chromosome inactivation patterns in the Rett syndrome brain
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Shahbazian MD, Sun Y, Zoghbi HY: Balanced X chromosome inactivation patterns in the Rett syndrome brain. Am J Med Genet 2002, 111:164-168.
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Am J Med Genet
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Shahbazian, M.D.1
Sun, Y.2
Zoghbi, H.Y.3
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13
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38949088605
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Skewed X chromosome inactivation failed to explain the normal phenotype of a carrier female with MECP2 mutation resulting in Rett syndrome
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This was an unusual case report describing the maternal transmission of an RTT-causing MECP2 mutation and skewed XCI; however, the mother's preferentially inactivated allele was the wild-type allele and could not explain the apparently normal phenotype of the mother
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Takahashi S, Ohinata J, Makita Y, et al.: Skewed X chromosome inactivation failed to explain the normal phenotype of a carrier female with MECP2 mutation resulting in Rett syndrome. Clin Genet 2008, 73:257-261. This was an unusual case report describing the maternal transmission of an RTT-causing MECP2 mutation and skewed XCI; however, the mother's preferentially inactivated allele was the wild-type allele and could not explain the apparently normal phenotype of the mother.
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Clin Genet
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Takahashi, S.1
Ohinata, J.2
Makita, Y.3
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14
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37449007840
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X chromosome inactivation in Rett syndrome and its correlations withMECP2mutations and phenotype
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This was a thorough investigation of XCI in RTT phenotype in 52 RTT cases, 50 RTT mothers, and 48 control females showing that XCI skewing and genotype are insufficient to explain the phenotypic manifestations of RTT
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Bao X, Jiang S, Song F, et al.: X chromosome inactivation in Rett syndrome and its correlations withMECP2mutations and phenotype. J Child Neurol 2008, 23:22-25. This was a thorough investigation of XCI in RTT phenotype in 52 RTT cases, 50 RTT mothers, and 48 control females showing that XCI skewing and genotype are insufficient to explain the phenotypic manifestations of RTT.
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(2008)
J Child Neurol
, vol.23
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Bao, X.1
Jiang, S.2
Song, F.3
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16
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85047697344
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Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy
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Topcu M, Akyerli C, Sayi A, et al.: Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy. Eur J Hum Genet 2002, 10:77-81.
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Eur J Hum Genet
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Topcu, M.1
Akyerli, C.2
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67649921127
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The genetic landscape of intellectual disability arising from chromosome X
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Gecz J, Shoubridge C, Corbett M: The genetic landscape of intellectual disability arising from chromosome X. Trends Genet 2009, 25:308-316.
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Gecz, J.1
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18
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0035870846
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MECP2 is highly mutated in X-linked mental retardation
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Couvert P, Bienvenu T, Aquaviva C, et al.: MECP2 is highly mutated in X-linked mental retardation. Hum Mol Genet 2001, 10:941-946.
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Hum Mol Genet
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Couvert, P.1
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Aquaviva, C.3
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19
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62849107557
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Structural variation in Xq28: MECP2 duplications in 1% of patients with unexplained XLMR and in 2% of male patients with severe encephalopathy
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(Published erratum appears in Eur J Hum Genet 2009, 17:697.) MECP2 duplications were found in about 1% of male patients with unexplained XLMR and as many as 2% of patients with severe progressive neurologic symptoms In contrast, no MECP2 duplications were observed in 329 female patients
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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. (Published erratum appears in Eur J Hum Genet 2009, 17:697.) MECP2 duplications were found in about 1% of male patients with unexplained XLMR and as many as 2% of patients with severe progressive neurologic symptoms. In contrast, no MECP2 duplications were observed in 329 female patients.
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(2009)
Eur J Hum Genet
, vol.17
, pp. 444-453
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Lugtenberg, D.1
Kleefstra, T.2
Oudakker, A.R.3
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20
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23944503759
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Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males
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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.
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Am J Hum Genet
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Van Esch, H.1
Bauters, M.2
Ignatius, J.3
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21
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0038626842
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Identification of MeCP2 mutations in a series of females with autistic disorder
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Carney RM, Wolpert CM, Ravan SA, et al.: Identification of MeCP2 mutations in a series of females with autistic disorder. Pediatr Neurol 2003, 28:205-211.
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Carney, R.M.1
Wolpert, C.M.2
Ravan, S.A.3
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22
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52949128317
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Methyl-CpG-binding protein 2 polymorphisms and vulnerability to autism
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Loat CS, Curran S, Lewis CM, et al.: Methyl-CpG-binding protein 2 polymorphisms and vulnerability to autism. Genes Brain Behav 2008, 7:754-760.
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Genes Brain Behav
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Loat, C.S.1
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Lewis, C.M.3
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23
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34247095504
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Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrantMECP2 promoter methylation
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Nagarajan RP, Hogart AR, Gwye Y, et al.: Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrantMECP2 promoter methylation. Epigenetics 2006, 1:e1-e11.
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Epigenetics
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Nagarajan, R.P.1
Hogart, A.R.2
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24
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3042847437
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MECP2 structural and 3'-UTR variants in schizophrenia, autism and other psychiatric diseases: A possible association with autism
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Shibayama A, Cook EH Jr, Feng J, et al.: MECP2 structural and 3'-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. Am J Med Genet B Neuropsychiatr Genet 2004, 128B:50-53.
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Am J Med Genet B Neuropsychiatr Genet
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Shibayama, A.1
Cook Jr., E.H.2
Feng, J.3
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25
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66149139048
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Autism and other neuropsychiatric symptoms are prevalent in individuals with MECP2duplication syndrome
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This was a thorough clinical and neuropsychiatric assessment of affected boys with MECP2 mutations and their carrier mothers showing that all boys with MECP2 duplication boys had autism, whereas female carriers showed a variety of psychiatric symptoms despite exhibiting skewed XCI
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Ramocki M, Sarika UP, Tavyev YJ, et al.: Autism and other neuropsychiatric symptoms are prevalent in individuals with MECP2duplication syndrome. Ann Neurology 2009, 66:771-782. This was a thorough clinical and neuropsychiatric assessment of affected boys with MECP2 mutations and their carrier mothers showing that all boys with MECP2 duplication boys had autism, whereas female carriers showed a variety of psychiatric symptoms despite exhibiting skewed XCI.
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(2009)
Ann Neurology
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Ramocki, M.1
Sarika, U.P.2
Tavyev, Y.J.3
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27
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58049116929
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A novel hypomorphic MECP2 point mutation is associated with a neuropsychiatric phenotype
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Adegbola AA, Gonzales ML, Chess A, et al.: A novel hypomorphic MECP2 point mutation is associated with a neuropsychiatric phenotype. Hum Genet 2009, 124:615-623.
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Adegbola, A.A.1
Gonzales, M.L.2
Chess, A.3
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28
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0036371289
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MECP2 mutation in a boy with language disorder and schizophrenia
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Cohen D, Lazar G, Couvert P, et al.: MECP2 mutation in a boy with language disorder and schizophrenia. Am J Psychiatry 2002, 159:148-149.
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Am J Psychiatry
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Cohen, D.1
Lazar, G.2
Couvert, P.3
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29
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0035054930
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Angelman syndrome phenotype associated with mutations in MECP2, a gene encoding a methyl CpG binding protein
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Watson P, Black G, Ramsden S, et al.: Angelman syndrome phenotype associated with mutations in MECP2, a gene encoding a methyl CpG binding protein. J Med Genet 2001, 38:224-228.
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J Med Genet
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Watson, P.1
Black, G.2
Ramsden, S.3
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30
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0031837109
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Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
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Jones PL, Veenstra GJ, Wade PA, et al.: Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 1998, 19:187-191.
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Jones, P.L.1
Veenstra, G.J.2
Wade, P.A.3
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31
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11244328520
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Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome
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Horike S, Cai S, Miyano M, et al.: Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome. Nat Genet 2005, 37:31-40.
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(2005)
Nat Genet
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Horike, S.1
Cai, S.2
Miyano, M.3
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32
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37649022627
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Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes
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This ChIP-chip and epigenomic analysis of MeCP2 binding sites in tiled genomic regions and promoters genome wide challenged the expectation that MeCP2 would be primarily bound to inactive gene promoters
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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. This ChIP-chip and epigenomic analysis of MeCP2 binding sites in tiled genomic regions and promoters genome wide challenged the expectation that MeCP2 would be primarily bound to inactive gene promoters.
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(2007)
Proc Natl Acad Sci USA
, vol.104
, pp. 19416-19421
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Yasui, D.H.1
Peddada, S.2
Bieda, M.C.3
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33
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45849105557
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MeCP2, a key contributor to neurological disease, activates and represses transcription
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This study showed that MeCP2 associates with the transcriptional activator CREB1 and for most identified target genes activated rather than repressed expression
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Chahrour M, Jung SY, Shaw C, et al.: MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008, 320:1224-1229. This study showed that MeCP2 associates with the transcriptional activator CREB1 and for most identified target genes activated rather than repressed expression.
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(2008)
Science
, vol.320
, pp. 1224-1229
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Chahrour, M.1
Jung, S.Y.2
Shaw, C.3
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34
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33749590330
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Brain-specific phosphorylation of MeCP2 regulates activity-dependent BDNF transcription, dendritic growth, and spine maturation
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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.
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(2006)
Neuron
, vol.52
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Zhou, Z.1
Hong, E.J.2
Cohen, S.3
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35
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0037081840
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Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation
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Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY: Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet 2002, 11:115-124.
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Hum Mol Genet
, vol.11
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Shahbazian, M.D.1
Antalffy, B.2
Armstrong, D.L.3
Zoghbi, H.Y.4
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36
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0037280319
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Elevated methyl- CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation
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Balmer D, Goldstine J, Rao YM, LaSalle JM: Elevated methyl- CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation. J Mol Med 2003, 81:61-68.
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J Mol Med
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Balmer, D.1
Goldstine, J.2
Rao, Y.M.3
LaSalle, J.M.4
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37
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41149136769
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Selective cerebral volume reduction in Rett syndrome: A multiple-approach MR imaging study
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Carter JC, Lanham DC, Pham D, et al.: Selective cerebral volume reduction in Rett syndrome: a multiple-approach MR imaging study. AJNR Am J Neuroradiol 2008, 29:436-441.
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AJNR Am J Neuroradiol
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Carter, J.C.1
Lanham, D.C.2
Pham, D.3
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38
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60749102039
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Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology
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This study showed that MeCP2 is expressed in astrocytes, and glial MeCP2 deficiency contributed to neuronal dendritic morphology defects in a murine model of RTT
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Ballas N, Lioy DT, Grunseich C, Mandel G: Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci 2009, 12:311-317. This study showed that MeCP2 is expressed in astrocytes, and glial MeCP2 deficiency contributed to neuronal dendritic morphology defects in a murine model of RTT.
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(2009)
Nat Neurosci
, vol.12
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Ballas, N.1
Lioy, D.T.2
Grunseich, C.3
Mandel, G.4
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39
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65549144456
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Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions
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This study also showed glial expression and the importance of astrocytes in RTT pathogenesis by spreading MeCP2 deficiency through gap junctions
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Maezawa I, Swanberg S, Harvey D, et al.: Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci 2009, 29:5051-5061. This study also showed glial expression and the importance of astrocytes in RTT pathogenesis by spreading MeCP2 deficiency through gap junctions.
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(2009)
J Neurosci
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, pp. 5051-5061
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Maezawa, I.1
Swanberg, S.2
Harvey, D.3
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40
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0035093830
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Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rettlike phenotype in mice
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Chen RZ, Akbarian S, Tudor M, Jaenisch R: Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rettlike phenotype in mice. Nat Genet 2001, 27:327-331.
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Nat Genet
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Chen, R.Z.1
Akbarian, S.2
Tudor, M.3
Jaenisch, R.4
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41
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0035094767
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A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome
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Guy J, Hendrich B, Holmes M, et al.: A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 2001, 27:322-326.
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Nat Genet
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Guy, J.1
Hendrich, B.2
Holmes, M.3
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42
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0037130455
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Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3
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Shahbazian M, Young J, Yuva-Paylor L, et al.: Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 2002, 35:243-254.
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Neuron
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Shahbazian, M.1
Young, J.2
Yuva-Paylor, L.3
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43
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1942533500
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Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice
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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.
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Proc Natl Acad Sci USA
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Luikenhuis, S.1
Giacometti, E.2
Beard, C.F.3
Jaenisch, R.4
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44
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33846924001
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Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2
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A transgenic gene therapy approach in mice resulted in a partial rescue of RTT phenotype when Mecp2 was expressed postnatally under an inducible promoter
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Giacometti E, Luikenhuis S, Beard C, Jaenisch R: Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad SciUSA2007, 104:1931-1936. A transgenic gene therapy approach in mice resulted in a partial rescue of RTT phenotype when Mecp2 was expressed postnatally under an inducible promoter.
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Proc Natl Acad Sci USA
, vol.104
, pp. 1931-1936
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Giacometti, E.1
Luikenhuis, S.2
Beard, C.3
Jaenisch, R.4
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45
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33847266846
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Reversal of neurological defects in a mouse model of Rett syndrome
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This study showed a strong rescue effect in a Mecp2-deficient mouse with removable Stop codon. An improvement in neurological symptoms was observed with restored Mecp2 expression, even for previously symptomatic mice, providing hope that RTT and other MECP2-associated disorders may be treatable after birth in humans
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Guy J, Gan J, Selfridge J, et al.: Reversal of neurological defects in a mouse model of Rett syndrome. Science 2007, 315:1143-1147. This study showed a strong rescue effect in a Mecp2-deficient mouse with removable Stop codon. An improvement in neurological symptoms was observed with restored Mecp2 expression, even for previously symptomatic mice, providing hope that RTT and other MECP2-associated disorders may be treatable after birth in humans.
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Science
, vol.315
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Guy, J.1
Gan, J.2
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46
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8444253290
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Mild overexpression of MeCP2 causes a progressive neurological disorder in mice
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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.
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Hum Mol Genet
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Collins, A.L.1
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Vilaythong, A.P.3
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47
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30644479042
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Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome
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Moretti P, Levenson JM, Battaglia F, et al.: Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J Neurosci 2006, 26:319-327.
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J Neurosci
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Moretti, P.1
Levenson, J.M.2
Battaglia, F.3
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48
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70349086187
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Intact long-term potentiation but reduced connectivity between neocortical layer 5 pyramidal neurons in a mouse model of Rett syndrome
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Recordings of layer 5 cortical pyramidal neurons in slices of Mecp2- deficient mice showed that reduced excitatory synaptic connectivity, rather than the induction of long-term potentiation, was responsible for the decreased excitatory neurotransmission in RTT
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Dani VS, Nelson SB: Intact long-term potentiation but reduced connectivity between neocortical layer 5 pyramidal neurons in a mouse model of Rett syndrome. J Neurosci 2009, 29:11263-11270. Recordings of layer 5 cortical pyramidal neurons in slices of Mecp2- deficient mice showed that reduced excitatory synaptic connectivity, rather than the induction of long-term potentiation, was responsible for the decreased excitatory neurotransmission in RTT.
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(2009)
J Neurosci
, vol.29
, pp. 11263-11270
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Dani, V.S.1
Nelson, S.B.2
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49
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0037488244
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Heterogeneity in residual function of MeCP2 carrying missense mutations in the methyl CpG binding domain
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Kudo S, Nomura Y, Segawa M, et al.: Heterogeneity in residual function of MeCP2 carrying missense mutations in the methyl CpG binding domain. J Med Genet 2003, 40:487-493.
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(2003)
J Med Genet
, vol.40
, pp. 487-493
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Kudo, S.1
Nomura, Y.2
Segawa, M.3
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50
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0036172191
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Functional characterisation of MeCP2 mutations found in male patients with X linked mental retardation
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Kudo S, Nomura Y, Segawa M, et al.: Functional characterisation of MeCP2 mutations found in male patients with X linked mental retardation. J Med Genet 2002, 39:132-136.
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(2002)
J Med Genet
, vol.39
, pp. 132-136
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Kudo, S.1
Nomura, Y.2
Segawa, M.3
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51
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65249169270
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The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome
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(Published erratum appears in Neurology 2009, 73:161.) This study reported that a common polymorphism of BDNF, a known MeCP2 target gene, was significantly associated with severity in R168X MECP2- mutant RTT patients, providing evidence for an independent genetic modifier effect
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Zeev BB, Bebbington A, Ho G, et al.: The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome. Neurology 2009, 72:1242-1247. (Published erratum appears in Neurology 2009, 73:161.) This study reported that a common polymorphism of BDNF, a known MeCP2 target gene, was significantly associated with severity in R168X MECP2- mutant RTT patients, providing evidence for an independent genetic modifier effect.
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(2009)
Neurology
, vol.72
, pp. 1242-1247
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Zeev, B.B.1
Bebbington, A.2
Ho, G.3
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