title: [Epigenetic study of Rett's syndrome as an adequate model for autistic disorders].
abstract: Rett's syndrome (RTT) is a severe hereditary disorder of the nervous system. MECP2 gene mutations are considered as a primary cause of the disease. In the present study, we have found MECP2 mutations in 33 (84.6%) out of 39 RTT females. We have also studied X-inactivation patterns in 70 girls with RTT. A frequency of skewed X-inactivation was 37% (26 patients), being significantly higher (p < 0.001) than that in the controls. The investigation of inactivated X chromosome origin revealed that about 33% pairs had preferentially the inactivated maternal X chromosome. An abnormal type of chromosome X inactivation was observed in all RTT females. Thus, we conclude that skewed X-inactivation may be considered as a common feature of RTT. There is unambiguous evidence that epigenetic alterations in RTT are associated with MECP2 mutations. MeCP2 protein also appears to be involved in transcriptional regulation of chromosome X genes. RTT in females without MECP2 mutations is related to the epigenetic alterations. We suggest X chromosome inactivation study in RTT females and their mothers to be informative for investigation of genetic processes in RTT girls, even in case MECP2 mutations have not been found. RTT could be considered as an appropriate model for studying epigenetic abnormalities in relation to autistic spectrum disorders.
authors.forename: I Iu
authors.initials: IIu
authors.lastname: Iurov
authors.forename: S G
authors.initials: SG
authors.lastname: Vorsanova
authors.forename: V Iu
authors.initials: VIu
authors.lastname: Voinova-Ulas
authors.forename: L
authors.initials: L
authors.lastname: Villard
authors.forename: I A
authors.initials: IA
authors.lastname: Demidova
authors.forename: L
authors.initials: L
authors.lastname: Giunti
authors.forename: M L
authors.initials: ML
authors.lastname: Guivabyccu-Uzielli
authors.forename: A V
authors.initials: AV
authors.lastname: Budilov
authors.forename: A K
authors.initials: AK
authors.lastname: Beresheva
authors.forename: P V
authors.initials: PV
authors.lastname: Novikov
authors.forename: Iu V
authors.initials: IuV
authors.lastname: Iurov
mesh_terms: D002648:Child; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2; D009035:Mothers; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics*; D012984:Software
chemical_list: C410798:AR protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D011944:Receptors, Androgen; D012097:Repressor Proteins