Rare Diseases of Neurodevelopment: Maintain the Mystery or Use a Dazzling Tool for Investigation? The Case of Rett Syndrome

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 of the electrophysiology has been performed on these models of diseases.On the other hand, the technique of membrane microtransplantation in Xenopus oocytes allows the study of human functional neurotransmitter receptors thanks to the use of tissues from autopsies or surgeries, even in quantities that would not permit other kinds of functional studies.In this short article, we intend to underline how this technique is well-fit for the study of rare diseases by characterizing the electrophysiological properties of GABAA and AMPA receptors in Rett syndrome. For our purposes, we used both tissues from Rett syndrome patients and Mecp2-null mice, a well validated murine model of the same disease, in order to strengthen the solidity of our results through the comparison of the two.Our findings retrace previous results and, in the light of this, further argue in fav...
Source: Neuroscience - Category: Neuroscience Source Type: research

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CONCLUSION: Integrative analysis of omics data and prior knowledge databases is a powerful approach to identify links between mutation and phenotype especially in rare disease research where little data is available. PMID: 30907210 [PubMed - as supplied by publisher]
Source: The World Journal of Biological Psychiatry - Category: Psychiatry Authors: Tags: World J Biol Psychiatry Source Type: research
In conclusion, a large number of approaches based on targeting microRNAs and long non-coding RNAs are expected in the field of molecular diagnosis and therapy, with a facilitated technological transfer in the case of rare genetic diseases, in virtue of the existing regulation concerning these diseases.
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research
VIII World Rett Syndrome Congress&Symposium of Rare Diseases was held in Kazan, Russia from 13 to 17 May 2016. Although it has been a while since the event, specific problems highlighted by the contributors ...
Source: Molecular Cytogenetics - Category: Molecular Biology Authors: Tags: Review Source Type: research
Complex neurodevelopmental disorders need multi-disciplinary treatment approaches for optimal care. The clinical effectiveness of treatments is limited in patients with rare genetic syndromes with multisystem ...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Review Source Type: research
The mechanisms of neuro-genetic disorders have been mostly investigated in the brain, however, for some pathologies, transcriptomic analysis in multiple tissues represent an opportunity and a challenge to unde...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Review Source Type: research
Rett syndrome: a seminal book on extensive multidisciplinary analyses for rare disease, Published online: 25 May 2018; doi:10.1038/s41431-018-0163-xRett syndrome: a seminal book on extensive multidisciplinary analyses for rare disease
Source: European Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
The reversal of the Rett syndrome disease process in the Mecp2 mouse model of Guy et al. (2007) has motivated families and researchers to work on this condition. The reversibility in adult mice suggests that t...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Position statement Source Type: research
Rett syndrome is caused by a pathogenic mutation in the MECP2 gene with major consequences for motor and cognitive development. One of the effects of impaired MECP2 function is reduced production of Brain Derived...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Research Source Type: research
In this study, we generated a mouse line carrying deletion of eight conserved amino acids in AT-hook 1 domain by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. Mecp2 ΔAT-hook1/y mutant male mice exhibited low locomotor activity, motor incoordination and cognitive deficit. In addition, these mutant mice exhibited increased anxiety. Moreover, pain insensitivity was noted in the mutant males. However, the social interactions were unaffected in AT-hook 1 mutant mice. Thinner CA1 region of the hippocampus was observed in the mutant mice. On the molecular basis, Western blot analysis sh...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Conclusion This tool offers new perspectives in a translational context to identify patients for genetic research. Moreover, when new molecular bases are discovered, our strategy will help to identify additional eligible patients for genetic screening. Graphical abstract
Source: Journal of Biomedical Informatics - Category: Information Technology Source Type: research
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