Unraveling Molecular Pathways Altered in MeCP2-Related Syndromes, in the Search for New Potential Avenues for Therapy
Por:
Castells AA, Balada R, Tristan-Noguero A, O'Callaghan-Gordo M, Cortés-Saladelafont E, Pascual-Alonso A, Garcia-Cazorla A, Armstrong-Moron J and Alcántara S
Publicada:
1 feb 2021
Ahead of Print:
3 feb 2021
Resumen:
Methyl-CpG-binding protein 2 (MeCP2) is an X-linked epigenetic modulator whose dosage is critical for neural development and function. Loss-of-function mutations in MECP2 cause Rett Syndrome (RTT, OMIM #312750) while duplications in the Xq28 locus containing MECP2 and Interleukin-1 receptor-associated kinase 1 (IRAK1) cause MECP2 duplication syndrome (MDS, OMIM #300260). Both are rare neurodevelopmental disorders that share clinical symptoms, including intellectual disability, loss of speech, hand stereotypies, vasomotor deficits and seizures. The main objective of this exploratory study is to identify novel signaling pathways and potential quantitative biomarkers that could aid early diagnosis and/or the monitoring of disease progression in clinical trials. We analyzed by RT-PCR gene expression in whole blood and microRNA (miRNA) expression in plasma, in a cohort of 20 females with Rett syndrome, 2 males with MECP2 duplication syndrome and 28 healthy controls, and correlated RNA expression with disease and clinical parameters. We have identified a set of potential biomarker panels for RTT diagnostic and disease stratification of patients with microcephaly and vasomotor deficits. Our study sets the basis for larger studies leading to the identification of specific miRNA signatures for early RTT detection, stratification, disease progression and segregation from other neurodevelopmental disorders. Nevertheless, these data will require verification and validation in further studies with larger sample size including a whole range of ages.
Filiaciones:
Castells AA:
Neural Development Lab, Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, l'Hospitalet de Llobregat, 08907 Barcelona, Spain
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
IDIBELL, l'Hospitalet de Llobregat, 08908 Barcelona, Spain
Balada R:
Neural Development Lab, Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, l'Hospitalet de Llobregat, 08907 Barcelona, Spain
IDIBELL, l'Hospitalet de Llobregat, 08908 Barcelona, Spain
Tristan-Noguero A:
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
O'Callaghan-Gordo M:
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
Cortés-Saladelafont E:
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
Pascual-Alonso A:
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
Garcia-Cazorla A:
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
Armstrong-Moron J:
Departments of Neurology, Biochemistry and Genetics, Institut Pediàtric de Recerca, CIBERER and ISCIII, Hospital San Joan de Déu, Esplugues de Llobregat, 08950 Barcelona, Spain
Alcántara S:
Neural Development Lab, Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, l'Hospitalet de Llobregat, 08907 Barcelona, Spain
IDIBELL, l'Hospitalet de Llobregat, 08908 Barcelona, Spain
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