Academic Journal
X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients
| العنوان: | X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients |
|---|---|
| المؤلفون: | Xiol, Clara, Vidal, Sílvia, Pascual-Alonso, Ainhoa, Blasco, Laura, Brandi, Núria, Pacheco, Paola, Rett Working Group |
| المساهمون: | Xiol C, Vidal S, Pascual-Alonso A, Blasco L, Pacheco P Molecular and Genetics Medicine Section, Hospital Sant Joan de Déu, Barcelona, Spain. Brandi N Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Rett, Síndrome de, Transcripció genètica - Regulació, Cromosoma X, DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Congenital, Inborn::Heredodegenerative Disorders, Nervous System::Mental Retardation, X-Linked::Rett Syndrome, PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic::Dosage Compensation, Genetic::X Chromosome Inactivation, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Amino Acids, and Proteins::Proteins::Nuclear Proteins::Chromosomal Proteins, Non-Histone::Amino Acids, and Proteins::Proteins::Methyl-CpG-Binding Protein 2, ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::trastornos heredodegenerativos del sistema nervioso::retraso mental ligado al cromosoma X::síndrome de Rett, FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética::compensación de dosis genética::inactivación del cromosoma X, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::aminoácidos, péptidos y proteínas::proteínas::nucleoproteínas::proteínas cromosómicas no histona::proteína 2 de unión a metil-CpG |
| الوصف: | Rett syndrome; X chromosome inactivation; MECP2 gene ; Síndrome de Rett; Inactivación del cromosoma X; Gen MECP2 ; Síndrome de Rett; Inactivació del cromosoma X; Gen MECP2 ; Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern. ; The work was supported by grants from the Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER, PI15/01159); Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundacion Espanola para la Ciencia y la Tecnologia); the Catalan Association for Rett Syndrome; Fondobiorett and Mi Princesa Rett. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | Scientific Reports;9(1); https://www.nature.com/articles/s41598-019-48385-w; info:eu-repo/grantAgreement/ES/PE2013-2016/PI15%2F01159; Xiol C, Vidal S, Pascual-Alonso A, Blasco L, Brandi N, Pacheco P, et al. X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients. Sci Rep. 2019 Aug 19;9(1):11983.; https://hdl.handle.net/11351/4699; 000481590200024 |
| DOI: | 10.1038/s41598-019-48385-w |
| الاتاحة: | https://hdl.handle.net/11351/4699 https://doi.org/10.1038/s41598-019-48385-w |
| Rights: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.4CFD5364 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-019-48385-w |