Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene

Autor: T. Lourenço, Anabela Silva-Fernandes, Maria Vânia Sousa, Teresa Temudo, Bauke Ylstra, Bruno M. Costa, Sofia Moura, José Pedro Vieira, Susana Palma de Sousa, Patrícia Maciel, Mafalda Barbosa, Fátima Lopes
Přispěvatelé: Pathology, CCA - Innovative therapy, Universidade do Minho
Rok vydání: 2015
Předmět:
congenital
hereditary
and neonatal diseases and abnormalities
Methyl-CpG-Binding Protein 2
Medicina Básica [Ciências Médicas]
Neurodevelopment
CDKL5
Intellectual disability
Rett syndrome
HDE NEU PED
Biology
Protein Serine-Threonine Kinases
X-inactivation
MECP2
Epigenesis
Genetic
03 medical and health sciences
0302 clinical medicine
Developmental Neuroscience
Intellectual Disability
mental disorders
medicine
Rett Syndrome
Humans
Epigenetics
RNA
Messenger
Child
X chromosome
030304 developmental biology
Chromosomal inversion
Genetics
0303 health sciences
Chromosomes
Human
X
Science & Technology
Epilepsy
medicine.disease
Fold change
3. Good health
nervous system diseases
Karyotyping
Chromosome Inversion
Mutation
Ciências Médicas::Medicina Básica
Neurodevelopmental
Female
030217 neurology & neurosurgery
Developmental Biology
Zdroj: International Journal of Developmental Neuroscience, 46, 82-87. Elsevier Limited
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Agência para a Sociedade do Conhecimento (UMIC)-FCT-Sociedade da Informação
instacron:RCAAP
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
Vieira, J P, Lopes, F, Silva-Fernandes, A, Sousa, M V, Moura, S, Sousa, S, Costa, B M, Barbosa, M, Ylstra, B, Temudo, T, Lourenco, T & Maciel, P 2015, ' Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene ', International Journal of Developmental Neuroscience, vol. 46, pp. 82-87 . https://doi.org/10.1016/j.ijdevneu.2015.07.010
ISSN: 0736-5748
DOI: 10.1016/j.ijdevneu.2015.07.010
Popis: Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55 +/- 038) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98 +/- 0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the de-regulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic de-regulation of the MECP2 may be present in other RTT-like patients.
info:eu-repo/semantics/publishedVersion
Databáze: OpenAIRE
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