Caracterización de nuevas variantes en los genes MECP2 y CDKL5 en pacientes con Síndrome de Rett


Rodríguez Mesa, Noelia  


Rett syndrome (RTT) is a neurodevelopmental disorder that affects one in 10,000 to 15,000 women worldwide. RTT is largely due to mutations in the MECP2 gene, located on the X chromosome and encoding a protein that binds to other genes thus regulating transcription.
The variety of girls ’phenotypes is due to the sum of the different resulting alterations in the MeCP2 protein along with the X chromosome inactivation pattern in each organism and cellular tissue, which will be discussed during the project. However, it should be noted that today there is no solid genotype-phenotype relationship.
RTT is characterized by a regression of development that includes the loss of expressive language and intentional use of the hands with the emergence of stereotypical movements of these. Individuals with RTT have motor deficiencies and other systemic, autonomic, and gastrointestinal symptoms.For now, there is no approved or effective treatment available for prevalent symptoms of RTT, but at the Hospital Sant Joan de Déu in Barcelona there are three projects currently underway, all co-financed by Biorett funds and supervised by Dra. Mercè Pineda. The first works with markers of synaptic dysfunction in Rett syndrome, and studies the synapse of patients to normalize it. The second is responsible for the analysis of behavioral disorders, with the aim of reducing, for example, pharmacological anxiety. These two are led by Dra. Àngels García-Cazorla. The third project is led by Dra. Judith Armstrong and studies RTT at the genetic level. It is essential to know the genes that cause this syndrome and the type of mutation to address gene, protein or pharmacological therapy. Apart from the MECP2 gene, there are some more that produce Rett syndrome, such as FoxG1 and CDKL5. During the study, six cases of patients from Sant Joan de Déu Hospital were studied, three of them with a variant in MECP2, and the remaining three with deletions in CDKL5. It is studied whether these variants in these genes in men with asymptomatic mothers are the causes of the clinical picture presented by the child. In some cases, the mothers of patients are seemingly healthy carriers, although they may have a mild intellectual disability. This is because both MECP2 and CDKL5 are located on the X chromosome and women, in this case, asymptomatic mothers, are subject to X chromosome inactivation.
To achieve the above-mentioned goal, first, an in silico approach is made, where databases and prediction programs are used for each of the variants in MECP2 and CDKL5, making a report of how pathogenic it is believed. which may be this variant. Second, laboratory experiments are designed to be able to validate the results in silico. Finally, the initial plan was to implement these experiments, but due to the situation we are going through with Covidien-19, it has not been possible to perform this last point.



Fornaguera Puigvert, Cristina 
Armstrong, Judith  


IQS SE - Undergraduate Program in Biotechnology