Top

Published in:

Open Access 01-12-2018 | Review

Transcriptome level analysis in Rett syndrome using human samples from different tissues

Authors: Stephen Shovlin, Daniela Tropea

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

Abstract

The mechanisms of neuro-genetic disorders have been mostly investigated in the brain, however, for some pathologies, transcriptomic analysis in multiple tissues represent an opportunity and a challenge to understand the consequences of the genetic mutation. This is the case for Rett Syndrome (RTT): a neurodevelopmental disorder predominantly affecting females that is characterised by a loss of purposeful movements and language accompanied by gait abnormalities and hand stereotypies. Although the genetic aetiology is largely associated to Methyl CpG binding protein 2 (MECP2) mutations, linking the pathophysiology of RTT and its clinical symptoms to direct molecular mechanisms has been difficult.

One approach used to study the consequences of MECP2 dysfunction in patients, is to perform transcriptomic analysis in tissues derived from RTT patients or Induced Pluripotent Stem cells. The growing affordability and efficiency of this approach has led to a far greater understanding of the complexities of RTT syndrome but is also raised questions about previously held convictions such as the regulatory role of MECP2, the effects of different molecular mechanisms in different tissues and role of X Chromosome Inactivation in RTT.

In this review we consider the results of a number of different transcriptomic analyses in different patients-derived preparations to unveil specific trends in differential gene expression across the studies. Although the analyses present limitations- such as the limited sample size- overlaps exist across these studies, and they report dysregulations in three main categories: dendritic connectivity and synapse maturation, mitochondrial dysfunction, and glial cell activity.

These observations have a direct application to the disorder and give insights on the altered mechanisms in RTT, with implications on potential diagnostic criteria and treatments.

Neul JL, Kaufmann WE, Glaze DG, Clarke AJ, Leonard H, Bailey MES, et al. Rett syndrome: revised diagnostic criteria and Nomenlcature. Ann Neurol. 2010;68:944–50. https://doi.org/10.1002/ana.22124.Rett.CrossRefPubMedPubMedCentral

Archer HL, Evans J, Edwards S, Colley J, Newbury-Ecob R, O’Callaghan F, et al. CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients. J Med Genet 2006;43:729–734. doi:jmg.2006.041467.

Renieri A, Mari F, Mencarelli MA, Scala E, Ariani F, Longo I, et al. Diagnostic criteria for the Zappella variant of Rett syndrome (the preserved speech variant). Brain and Development. 2009;31:208–16. https://doi.org/10.1016/j.braindev.2008.04.007.CrossRefPubMed

Takagi M, Sasaki G, Mitsui T, Honda M, Tanaka Y, Hasegawa T. A 2.0Mb microdeletion in proximal chromosome 14q12, involving regulatory elements of FOXG1, with the coding region of FOXG1 being unaffected, results in severe developmental delay, microcephaly, and hypoplasia of the corpus callosum. Eur J Med Genet. 2013;56:526–8. https://doi.org/10.1016/j.ejmg.2013.05.012.CrossRefPubMed

Hagberg B, Rasmussen P. “FORME FRUSTE” of RETT syndrome - a CASE report. Am J Med Genet. 1986;181:175–81.

Pini G, Bigoni S, Congiu L, Romanelli a M, Scusa MF, Di Marco P, et al. Rett syndrome: a wide clinical and autonomic picture. Orphanet J Rare Dis. 2016;11:132. https://doi.org/10.1186/s13023-016-0499-7.CrossRefPubMedPubMedCentral

Jan MMS, Dooley JM, Gordon KE. Male Rett syndrome variant: application of diagnostic criteria. Pediatr Neurol. 1999;20:238–40.CrossRefPubMed

Hagberg B. Clinical manifestations and stages of Rett syndrome. Ment Retard Dev Disabil Res Rev. 2002;8:61–5.CrossRefPubMed

Krishnaraj R, Ho G, Christodoulou J. RettBASE: Rett syndrome database update. Hum Mutat. 2017; July 2016:1–10. https://doi.org/10.1002/humu.23263.

10.

Percy AK, Lane JB, Childers J, Skinner S, Annese F, Barrish J, et al. Rett syndrome: north American database. J Child Neurol. 2007;22:1338–41. https://doi.org/10.1177/0883073807308715.CrossRefPubMed

11.

Suter B, Treadwell-Deering D, Zoghbi HY, Glaze DG, Neul JL. Brief report: MECP2 mutations in people without rett syndrome. J Autism Dev Disord. 2014;44:703–11.CrossRefPubMedPubMedCentral

12.

Fehr S, Wilson M, Downs J, Williams S, Murgia A, Sartori S, et al. The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy. Eur J Hum Genet. 2013;21:266–73. https://doi.org/10.1038/ejhg.2012.156.CrossRefPubMed

13.

Mangatt M, Wong K, Anderson B, Epstein A, Hodgetts S, Leonard H, et al. Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome. Orphanet J Rare Dis. 2016;11:1–16. https://doi.org/10.1186/s13023-016-0418-y. CrossRef

14.

Colak D, Al-Dhalaan H, Nester M, AlBakheet AB, Al-Younes B, Al-Hassnan Z, et al. Genomic and transcriptomic analyses distinguish classic Rett and Rett-like syndrome and reveals shared altered pathways. Genomics. 2011;97:19–28. https://doi.org/10.1016/j.ygeno.2010.09.004.CrossRefPubMed

15.

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;11:115–24.CrossRefPubMed

16.

Olson CO, Zachariah RM, Ezeonwuka CD, Liyanage VRB, Rastegar M. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements. PLoS One. 2014;9

17.

Sugino K, Hempel CM, Okaty BW, Arnson HA, Kato S, Dani VS, et al. Cell-type-specific repression by methyl-CpG-binding protein 2 is biased toward long genes. J Neurosci. 2014;34:12877–83. https://doi.org/10.1523/JNEUROSCI.2674-14.2014.

18.

Ross PD, Guy J, Selfridge J, Kamal B, Bahey N, Tanner E, et al. Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes. HMG Advance Access Hum Mol Genet. 2016;0:1–16. https://doi.org/10.1093/hmg/ddw269.CrossRef

19.

Zhao S, Fung-Leung WP, Bittner A, Ngo K, Liu X. Comparison of RNA-Seq and microarray in transcriptome profiling of activated T cells. PLoS One. 2014;9

20.

Xu J, Fang H, Hong H, Shen J, Su Z. A comprehensive study design reveals treatment- and transcript abundance-deprendent concordance between RNA-seq and microarray data 2014;32:926–32.

21.

Piper MDW, Daran-Lapujade P, Bro C, Regenberg B, Knudsen S, Nielsen J, et al. Reproducibility of oligonucleotide microarray transcriptome analyses. An interlaboratory comparison using chemostat cultures of Saccharomyces cerevisiae. J Biol Chem. 2002;277:37001–8.CrossRefPubMed

22.

Costa V, Aprile M, Esposito R, Ciccodicola A. RNA-Seq and human complex diseases: recent accomplishments and future perspectives. Eur J Hum Genet. 2012;21:134–42. https://doi.org/10.1038/ejhg.2012.129.CrossRefPubMedPubMedCentral

23.

Colantuoni C, Jeon OH, Hyder K, Chenchik A, Khimani AH, Narayanan V, et al. Gene expression profiling in postmortem Rett Syndromerain: differential gene expression and patient classification. Neurobiol Dis. 2001;8:847–65. https://doi.org/10.1006/nbdi.2001.0428.CrossRefPubMed

24.

Deng V, Matagne V, Banine F, Frerking M, Ohliger P, Budden S, et al. FXYD1 is an MeCP2 target gene overexpressed in the brains of Rett syndrome patients and Mecp2-null mice. Hum Mol Genet. 2007;16:640–50.CrossRefPubMed

25.

Gibson JH, Slobedman B, K N H, Williamson SL, Minchenko D, El-Osta a, et al. downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain. BMC Neurosci. 2010;11:53.CrossRefPubMedPubMedCentral

26.

Lin P, Nicholls L, Assareh H, Fang Z, Amos TG, Edwards RJ, et al. Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q genes in Rett syndrome. BMC Genomics. 2016:1–11. https://doi.org/10.1186/s12864-016-2746-7.

27.

Matagne V, Budden S, Ojeda SR, Raber J. Correcting deregulated Fxyd1 expression ameliorates a behavioral impairment in a mouse model of Rett syndrome. Brain Res. 2013;1496:104–14. https://doi.org/10.1016/j.brainres.2012.12.009.CrossRefPubMed

28.

Carter JC, Lanham DC, Pham D, Bibat G, Naidu S, Kaufmann WE. Selective cerebral volume reduction in Rett syndrome: a multiple-approach MR imaging study. Am J Neuroradiol. 2008;29:436–41.CrossRefPubMed

29.

Reiss AL, Faruque F, Naidu S, Abrams M, Beaty T, Bryan RN, et al. Neuroanatomy of Rett Syndrome : a VolumetIric Imagmg study. Ann Neurol. 1993;34:227–34.CrossRefPubMed

30.

Nuutinen T, Suuronen T, Kyrylenko S, Huuskonen J, Salminen A. Induction of clusterin/apoJ expression by histone deacetylase inhibitors in neural cells. Neurochem Int. 2005;47:528–38.CrossRefPubMed

31.

Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, et al. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 1998;19 june:187–191. doi:https://doi.org/10.1038/561.

32.

LeBlanc JJ, DeGregorio G, Centofante E, Vogel-Farley VK, Barnes K, Kaufmann WE, et al. Visual evoked potentials detect cortical processing deficits in Rett syndrome. Ann Neurol. 2015;78:775–86.CrossRefPubMed

33.

Ben-Shachar S, Chahrour M, Thaller C, Shaw CA, Zoghbi HY. Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus. Hum Mol Genet. 2009;18:2431–42.CrossRefPubMedPubMedCentral

34.

Pecorelli A, Leoni G, Cervellati F, Canali R, Signorini C, Leoncini S, et al. Genes related to mitochondrial functions, protein degradation, and chromatin folding are differentially expressed in lymphomonocytes of rett syndrome patients. Mediat Inflamm. 2013;2013

35.

De Felice C, Della Ragione F, Signorini C, Leoncini S, Pecorelli A, Ciccoli L, et al. Oxidative brain damage in Mecp2-mutant murine models of Rett syndrome. Neurobiol Dis. 2014;68:66–77. https://doi.org/10.1016/j.nbd.2014.04.006.CrossRefPubMedPubMedCentral

36.

Pecorelli A, Ciccoli L, Signorini C, Leoncini S, Giardini A, D’Esposito M, et al. Increased levels of 4HNE-protein plasma adducts in Rett syndrome. Clin Biochem. 2011;44:368–71. https://doi.org/10.1016/j.clinbiochem.2011.01.007.CrossRefPubMed

37.

Amm I, Sommer T, Wolf DH. Protein quality control and elimination of protein waste: the role of the ubiquitin-proteasome system. Biochim Biophys Acta - Mol Cell Res. 2014;1843:182–96. https://doi.org/10.1016/j.bbamcr.2013.06.031.CrossRef

38.

Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D. NF-κB functions in synaptic signaling and behavior. Nat Neurosci. 2003;6:1072–8. https://doi.org/10.1038/nn1110.CrossRefPubMed

39.

Park I-H, Lerou PH, Zhao R, Huo H, Daley GQ. Generation of human-induced pluripotent stem cells. Nat Protoc. 2008;3:1180–6. https://doi.org/10.1038/nprot.2008.92.CrossRefPubMed

40.

Marchetto MCNM, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, et al. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell. 2010;143:527–39. https://doi.org/10.1016/j.cell.2010.10.016.A. CrossRefPubMedPubMedCentral

41.

Kim K, Jaenisch R, Feinberg AP, Weissleder R, Kim J, Murakami P, et al. Epigenetic memory in induced pluripotent stem cells. Nature. 2010;467:285–90. https://doi.org/10.1038/nature09342.CrossRefPubMedPubMedCentral

42.

Cheung AYL, Horvath LM, Grafodatskaya D, Pasceri P, Weksberg R, Hotta A, et al. Isolation of MECP2-null Rett syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. Hum Mol Genet. 2011;20:2103–15.CrossRefPubMedPubMedCentral

43.

Pomp O, Dreesen O, Leong DFM, Meller-Pomp O, Tan TT, Zhou F, et al. Unexpected X chromosome skewing during culture and reprogramming of human somatic cells can be alleviated by exogenous telomerase. Cell Stem Cell. 2011;9:156–65. https://doi.org/10.1016/j.stem.2011.06.004.CrossRefPubMed

44.

Ananiev G, Williams EC, Li H, Chang Q. Isogenic pairs of wild type and mutant induced pluripotent stem cell (iPSC) lines from rett syndrome patients as in vitro disease model. PLoS One. 2011;6

45.

Cheung AYL, Horvath LM, Carrel L, Ellis J. X-chromosome inactivation in Rett syndrome human induced pluripotent stem cells. Front Psychiatry 2012;3 MAR:1–16.

46.

Polo JJM, Liu S, Figueroa MME, Kulalert W, Eminli S, Tan KY, et al. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol. 2010;28:848–55.CrossRefPubMedPubMedCentral

47.

Tanaka Y, Kim KY, Zhong M, Pan X, Weissman SM, Park IH. Transcriptional regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2). Hum Mol Genet. 2014;23:1045–55.CrossRefPubMed

48.

Papadimitriou JM, Hockey A, Tan N, Masters CL. Rett Syndrome : Abnormal Membrane-Bound Lamellated Inclusions in Neurons and Oligodendroglia. 1988;368.

49.

Jellinger K, Seitelberger F. Neuropathology of Rett syndrome. Am J Med Genet. 1986;24:259–88.CrossRef

50.

Kishi N, Macklis JD. MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci. 2004;27:306–21.CrossRefPubMed

51.

Belichenko PV, Wright EE, Belichenko NP, Masliah E, Li HH, Mobley WC, et al. Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of Rett syndrome: evidence for disruption of neuronal networks. J Comp Neurol. 2009;514:240–58.CrossRefPubMed

52.

Armstrong DD, Dunn K, Antalffy B. Decreased dendritic branching in frontal motor limbic cortex in Rett syndrome compared with trisomy 21. J Neuropathol Exp Neurol. 1998;57:1013–7.CrossRefPubMed

53.

Armstrong DD. Neuropathology of Rett syndrome. J Child Neurol. 2005;20:747–53. https://doi.org/10.1177/08830738050200090901%0A.

54.

Xu X, Miller EC, Pozzo-Miller L. Dendritic spine dysgenesis in Rett syndrome. Front Neuroanat 2014;8 September:97. doi:https://doi.org/10.3389/fnana.2014.00097.

55.

Kaufmann WE, Johnston MV, Blue ME. MeCP2 expression and function during brain development: implications for Rett syndrome’s pathogenesis and clinical evolution. Brain and Development. 2005;27(SUPPL. 1):77–87.CrossRef

56.

Kishi N, MacDonald JL, Ye J, Molyneaux BJ, Azim E, Macklis JD. Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice. Nat Commun. 2016;7:10520. https://doi.org/10.1038/ncomms10520.CrossRefPubMedPubMedCentral

57.

Sarnat HB. Clinical neuropathology practice guide 5-2013: markers of neuronal maturation. Clin Neuropathol. 2013;32:340–69. https://doi.org/10.5414/NP300638.CrossRefPubMedPubMedCentral

58.

He L, Liu N, Cheng T, Chen X, Li Y, Shu Y, et al. Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity. Nat Commun. 2014;5:5036. https://doi.org/10.1038/ncomms6036.CrossRefPubMed

59.

Nguyen MVC, Du F, Felice CA, Shan X, Nigam A, Mandel G, et al. MeCP2 is critical for maintainng mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain. J Neurosci. 2013;32:10021–34.CrossRef

60.

Eeg-Olofsson O, Al-Zuhair AGH, Teebi AS, Al-Essa MMN, Opitz JM, Reynolds JF. Rett syndrome: genetic clues based on mitochondrial changes in muscle. Am J Med Genet. 1989;32:142–4. https://doi.org/10.1002/ajmg.1320320131.CrossRefPubMed

61.

Cornford ME, Philippart M, Jacobs B, Scheibel AB, Vinters HV. Neuropathology of Rett syndrome: case report with neuronal and mitochondrial abnormalities in the brain. J Child Neurol. 1994;9:424–31. https://doi.org/10.1177/088307389400900419.CrossRefPubMed

62.

Coker SB, Melnyk AR. Rett syndorme and mitochondrial enzyme deficiencies. J Child Neurol. 1991;6:164–6.CrossRefPubMed

63.

E a S, Manfredi G. Neuronal degeneration and mitochondrial dysfunction. J Clin Invest. 2003;111:303–12.CrossRef

64.

L a E, Melov S, Panov a, Cottrell B a, Wallace DC. Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci U S A. 1999;96:4820–5.CrossRef

65.

Schulz JB, Lindenau J, Seyfried J, Dichgans J. Oxidative stress and neurodegeneration. Eur J Biochem. 2000;267:4904–11.CrossRefPubMed

66.

Kriaucionis S, Paterson A, Curtis J, Guy J, MacLeod N, Bird A. Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome. Mol Cell Biol. 2006;26:5033–42. https://doi.org/10.1128/MCB.01665-05.CrossRefPubMedPubMedCentral

67.

Sticozzi C, Belmonte G, Pecorelli A, Cervellati F, Leoncini S, Signorini C, et al. Scavenger receptor B1 post-translational modifications in Rett syndrome. FEBS Lett. 2013;587:2199–204. https://doi.org/10.1016/j.febslet.2013.05.042.CrossRefPubMed

68.

De Felice C, Ciccoli L, Leoncini S, Signorini C, Rossi M, Vannuccini L, et al. Systemic oxidative stress in classic Rett syndrome. Free Radic Biol Med. 2009;47:440–8. https://doi.org/10.1016/j.freeradbiomed.2009.05.016.CrossRefPubMed

69.

Li Y, Wang H, Muffat J, Cheng AW, Orlando DA, Lovén J, et al. Global transcriptional and translational repression in human-embryonic- stem-cell-derived rett syndrome neurons. Cell Stem Cell. 2013;13:446–58.CrossRefPubMedPubMedCentral

70.

Janc OA, Hüser MA, Dietrich K, Kempkes B, Menzfeld C, Hülsmann S, et al. Systemic radical scavenger treatment of a mouse model of Rett syndrome: merits and limitations of the vitamin E derivative Trolox. Front Cell Neurosci 2016;10 November:1–20. doi:https://doi.org/10.3389/fncel.2016.00266.

71.

Andoh-Noda T, Akamatsu W, Miyake K, Matsumoto T, Yamaguchi R, Sanosaka T, et al. Differentiation of multipotent neural stem cells derived from Rett syndrome patients is biased toward the astrocytic lineage. Mol Brain. 2015;8:31. https://doi.org/10.1186/s13041-015-0121-2.CrossRefPubMedPubMedCentral

72.

Großer E, Hirt U, Janc OA, Menzfeld C, Fischer M, Kempkes B, et al. Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome. Neurobiol Dis. 2012;48:102–14. https://doi.org/10.1016/j.nbd.2012.06.007.CrossRefPubMed

73.

Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SBG, Guyenet PG, et al. Wild type microglia arrest pathology in a mouse model of Rett syndrome. Nature. 2012;484:105–9.CrossRefPubMedPubMedCentral

74.

Lioy DT, Garg SK, Monaghan CE, Raber J, Foust KD, Kaspar BK, et al. A role for glia in the progression of Rett’s syndrome. Nature. 2011;475:497–500. https://doi.org/10.1038/nature10214.CrossRefPubMedPubMedCentral

75.

Jieqi W. A. PA. Wild-type microglia do not reverse pathology in mouse models of Rett syndrome. Nature. 2015;109:105–9.

76.

Maezawa. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci. 2009;29:5051–61.CrossRefPubMedPubMedCentral

77.

Ballas N, Lioy DT, Grunseich C, Mandel G. Non–cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci. 2009;12:311–7. https://doi.org/10.1038/nn.2275.CrossRefPubMedPubMedCentral

78.

Maezawa I, Jin LW. Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J Neurosci. 2010;30:5346–56. https://doi.org/10.1523/JNEUROSCI.5966-09.2010.CrossRefPubMedPubMedCentral

79.

Okabe Y, Takahashi T, Mitsumasu C, Ichiro KK, Tanaka E, Matsuishi T. Alterations of gene expression and glutamate clearance in astrocytes derived from an mecp2-null mouse model of rett syndrome. PLoS One. 2012;7

80.

Maragakis NJ, Dietrich J, Wong V, Xue H, Mayer-Proschel M, Rao MS, et al. Glutamate transporter expression and function in human glial progenitors. Glia. 2004;45:133–43.CrossRefPubMed

81.

Das SK, Dash R, Dasgupta S, Barral PM, Hedvat M, Diaz P, et al. Role of excitatory amino acid transporter-2 (EAAT2) and Glutamate in neurodegeneration: Opportunities for developing novel Theraputics. 2012;226:2484–2493.

82.

Xie Z, Harris-White ME, Wals PA, Frautschy SA, Finch CE, Morgan TE. Apolipoprotein J (clusterin) activates rodent microglia in vivo and in vitro. J Neurochem. 2005;93:1038–46.CrossRefPubMed

83.

Zhao X, Wang H, Sun G, Zhang J, Edwards NJ, Aronowski XJ. Neuronal Interleukin-4 as a Modulator of Microglial Pathways and Ischemic Brain Damage. J Neurosci. 2015;35:11281–91.CrossRefPubMedPubMedCentral

84.

Pecorelli A, Cervellati F, Belmonte G, Montagner G, Waldon P, Hayek J, et al. Cytokines profile and peripheral blood mononuclear cells morphology in Rett and autistic patients. Cytokine. 2016;77:180–8. https://doi.org/10.1016/j.cyto.2015.10.002.CrossRefPubMed

85.

Leoncini S, De Felice C, Signorini C, Zollo G, Cortelazzo A, Durand T, et al. Cytokine Dysregulation in MECP2- and CDKL5-related Rett syndrome: relationships with aberrant redox homeostasis, inflammation, and ??-3 PUFAs. Oxidative Med Cell Longev. 2015;2015

86.

Derecki NC, Cronk JC, Kipnis J. The role of microglia in brain maintenance: implications for Rett syndrome. Trends Immunol. 2013;34:144–50.CrossRefPubMed

87.

Colvin L, Leonard H, de Klerk N, Davis M, Weaving L, Williamson S, et al. Refining the phenotype of common mutations in Rett syndrome. J Med Genet. 2004;41:25–30.CrossRefPubMedPubMedCentral

88.

Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, et al. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008;70:1313–21.CrossRefPubMedPubMedCentral

89.

Cuddapah VA, Pillai RB, Shekar KV, Lane JB, Kathleen J, Skinner SA, et al. Methyl-CpG-bnding protein 2 (MECP2) mutation type is associated with disease severity in Rett Syndrome. J Med Genet. 2014;51:152–8. https://doi.org/10.1136/jmedgenet-2013-102113.Methyl-CpG-binding.CrossRefPubMedPubMedCentral

90.

Trappe R, Laccone F, Cobilanschi J, Meins M, Huppke P, Hanefeld F, et al. MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin. Am J Hum Genet. 2001;68:1093–101.CrossRefPubMedPubMedCentral

91.

Gold WA, Krishnaraj R, Ellaway C, Christodoulou J. Rett syndrome: a genetic update and clinical review focusing on comorbidities. ACS Chem Neurosci 2017;:acschemneuro.7b00346. doi:https://doi.org/10.1021/acschemneuro.7b00346.

92.

Dragich J, Houwink-Manville I, Schanen C. Rett syndrome: a surprising result of mutation in MECP2. Hum Mol Genet Rev. 2000;9:2365–75.CrossRef

93.

Nan X, Meehan RR, Bird A. Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res. 1993;21:4886–92.CrossRefPubMedPubMedCentral

94.

Nan X, Campoy FJ, Bird A. MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997;88:471–81.CrossRefPubMed

95.

Nan X, Tate P, Li E, Bird A. DNA methylation specifies chromosomal localization of MeCP2. Mol Cell Biol. 1996;16:414–21. https://doi.org/10.1128/MCB.16.1.414.CrossRefPubMedPubMedCentral

96.

Kudo S. Methyl-CpG-binding protein MeCP2 represses Sp1-activated transcription of the human leukosialin gene when the promoter is methylated. Mol Cell Biol. 1998;18:5492–9.CrossRefPubMedPubMedCentral

97.

Kifayathullah LA, Arunachalam JP, Bodda C, Agbemenyah HY, Laccone FA, Mannan AU. MeCP2 mutant protein is expressed in astrocytes as well as in neurons and localizes in the nucleus. Cytogenet Genome Res. 2010;129:290–7.CrossRefPubMed

98.

Baker SA, Lombardi LM, Zoghbi HY. Karyopherin α 3 and karyopherin α 4 proteins mediate the nuclear import of methyl-CpG binding protein 2. J Biol Chem. 2015;290:22485–93.CrossRefPubMedPubMedCentral

99.

Fabio RA, Colombo B, Russo S, Cogliati F, Masciadri M, Foglia S, et al. Recent insights into genotype-phenotype relationships in patients with Rett syndrome using a fine grain scale. Res Dev Disabil. 2014;35:2976–86. https://doi.org/10.1016/j.ridd.2014.07.031.CrossRefPubMed

100.

Schanen C, Houwink EJF, Dorrani N, Lane J, Everett R, Feng A, et al. Phenotypic manifestations ofMECP2 mutations in classical and atypical rett syndrome. Am J Med Genet. 2004;126A:129–40. https://doi.org/10.1002/ajmg.a.20571.

Title: Transcriptome level analysis in Rett syndrome using human samples from different tissues
Authors: Stephen Shovlin
Daniela Tropea
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-018-0857-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Transcriptome level analysis in Rett syndrome using human samples from different tissues

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

Next generation phenotyping using narrative reports in a rare disease clinical data warehouse

Long term substrate reduction therapy with ezetimibe alone or associated with statins in three adult patients with lysosomal acid lipase deficiency

Illustration of patient-reported outcome challenges and solutions in rare diseases: a systematic review in Cushing’s syndrome

A total pleural covering of absorbable cellulose mesh prevents pneumothorax recurrence in patients with Birt-Hogg-Dubé syndrome

Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype

Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex