Rett syndrome before regression: a time window of overlooked opportunities for diagnosis and intervention

Publication date: Available online 18 May 2019Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Livia Cosentino, Daniele Vigli, Francesca Franchi, Giovanni Laviola, Bianca De FilippisAbstractRett syndrome (RTT) is a rare neurological disorder primarily affecting females, causing severe cognitive, social, motor and physiological impairments for which no cure currently exists. RTT clinical diagnosis is based on the peculiar progression of the disease, since patients show an apparently normal initial development with a subsequent sudden regression at around 2 years of age. Accumulating evidences are rising doubts regarding the absence of early impairments, hence questioning the concept of regression. We reviewed the published literature addressing the pre-symptomatic stage of the disease in both patients and animal models with a particular focus on behavioral, physiological and brain abnormalities. The emerging picture delineates subtle, but reliable impairments that precede the onset of overt symptoms whose bases are likely set up already during embryogenesis. Some of the outlined alterations appear transient, suggesting compensatory mechanisms to occur in the course of development. There is urgent need for more systematic developmental analyses able to detect early pathological markers to be used as diagnostic tools and precocious targets of time-specific interventions.
Source: Neuroscience and Biobehavioral Reviews - Category: Neuroscience Source Type: research

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Condition:   Rett Syndrome Intervention:   Other: An extensive biological assessment Sponsor:   Assistance Publique Hopitaux De Marseille Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 5 July 2019Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Eric E. Smeets, Gillian S. Townend, Leopold M.G. Curfs
Source: Neuroscience and Biobehavioral Reviews - Category: Neuroscience Source Type: research
Publication date: Available online 5 July 2019Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Jeffrey Lorenz Neul
Source: Neuroscience and Biobehavioral Reviews - Category: Neuroscience Source Type: research
Abstract Elucidating the functions of a particular gene is paramount to the understanding of how its dysfunction contributes to disease. This is especially important when the gene is implicated in multiple different disorders. One such gene is methyl-CpG-binding protein 2 (MECP2), which has been most prominently associated with the neurodevelopmental disorder Rett syndrome, as well as major neuropsychiatric disorders such as autism and schizophrenia. Being initially identified as a transcriptional regulator that modulates gene expression and subsequently also shown to be involved in other molecular events, dysfunc...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Methods Mol Biol Source Type: research
We report 2 cases of girls withMECP2 gene variants who do not have typical clinical features of Rett syndrome except for intellectual disability and seizures. Both patients present with adipositas, macrocephalia, precocious puberty, and seizures. They have prominent eyebrows and a short neck as well as short and plump fingers. Sequencing by NGS revealed a novel variant c.1162_1172del; p.Pro388* in both patients.Mol Syndromol
Source: Molecular Syndromology - Category: Molecular Biology Source Type: research
Patients with Rett syndrome (RTT) have severe mental and physical disabilities. The majority of RTT patients carry a heterozygous mutation in methyl-CpG binding protein 2 (MECP2), a X-linked gene encoding an epigenetic factor crucial for normal nerve cell function. No curative therapy for RTT syndrome exists and cellular mechanisms are incompletely understood. Here, we developed a CRISPR/Cas9-mediated system that targets and corrects the disease relevant regions of the MECP2 exon 4 coding sequence. We achieved homologous recombination (HR) efficiencies of 20-30% in human cell lines and iPSCs. Furthermore, we successfully i...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
We report 2 cases of girls withMECP2 gene variants who do not have typical clinical features of Rett syndrome except for intellectual disability and seizures. Both patients present with adipositas, macrocephalia, precocious puberty, and seizures. They have prominent eyebrows and a short neck as well as short and plump fingers. Sequencing by NGS revealed a novel variant c.1162_1172del; p.Pro388* in both patients.Mol Syndromol
Source: Molecular Syndromology - Category: Molecular Biology Source Type: research
Publication date: Available online 26 June 2019Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Angelisa Frasca, Francesco Bedogni, Nicoletta Landsberger
Source: Neuroscience and Biobehavioral Reviews - Category: Neuroscience Source Type: research
Publication date: Available online 21 June 2019Source: NeuroscienceAuthor(s): Gabriele Ruffolo, Pierangelo Cifelli, Catarina Lourenço, Eleonora De Felice, Cristina Limatola, Ana M. Sebastião, Maria J. Diógenes, Eleonora Aronica, Eleonora PalmaAbstractThe investigation on neurotransmission function during normal and pathologic development is a pivotal component needed to understand the basic mechanisms underlying neurodevelopmental pathologies. To study these diseases, many animal models have been generated which allowed to face the limited availability of human tissues and, as a consequence, the most o...
Source: Neuroscience - Category: Neuroscience Source Type: research
Publication date: Available online 21 June 2019Source: NeuroscienceAuthor(s): Albert Sanfeliu, Walter E. Kaufmann, Michael Gill, Paolo Guasoni, Daniela TropeaAbstractRett Syndrome (RTT) is a neurological disorder mainly associated with mutations in the X-linked gene coding for the methyl-CpG binding protein 2 (MECP2). To assist in studying MECP2's function, researchers have generated Mecp2 mouse mutants showing that MECP2's product (MeCP2) mostly function as a transcriptional regulator. During the last two decades, these models have been used to determine the genes that are regulated by MeCP2, slowly dissecting the aetiolo...
Source: Neuroscience - Category: Neuroscience Source Type: research
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