Catalogue en ligne Centre d'Information et de Documentation <br>du CRA Rhône-Alpes

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Experimental Tools for the Identification of Specific Genes in Autism Spectrum Disorders and Intellectual Disability

Type de document :

texte imprimé

Auteurs :

Yiping SHEN, Auteur ; Xiaohong GONG, Auteur

Année de publication :

2016

Importance :

p.3-12

Langues :

Anglais (eng)

Mots-clés :

Autozygosity mapping Balanced translocation breakpoint mapping Candidate gene approach Copy number variations Exome sequencing Linkage analysis Next-generation sequencing Positional mapping Whole-genome sequencing

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Technological advancements for interrogating genomic variants continue to facilitate discoveries of the genetic causes of intellectual disability (ID) and autism spectrum disorders (ASD), both of which are neurodevelopmental disorders known to have a strong genetic basis. In this chapter we discuss the major methods and approaches that have had significant roles in revealing genes and genomic regions associated with ID and ASD. Linkage analysis followed by candidate gene sequencing and positional cloning in patients with genomic rearrangements have been largely responsible for the success of identifying X-linked and autosomal dominant ID/ASD genes. Autozygosity mapping has a unique role in identifying recessive ID/ASD genes. Exome and whole-genome sequencing has provided unprecedented power for genotyping, and the data have provided us with a broader understanding of the association of de novo variants with ID and ASD. We believe that a better understanding of the genetic underpinnings will lead to better diagnosis, management, and treatment for patients with ID and ASD.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00001-7

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Genetic Causes of Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Guillaume HUGUET, Auteur ; Thomas BOURGERON, Auteur

Année de publication :

2016

Importance :

p.13-24

Langues :

Anglais (eng)

Mots-clés :

Autism spectrum disorders CNV Heritability SNV Synapse Twin studies

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

In the past 30 years, twin studies have indicated a strong genetic contribution to autism spectrum disorders (ASD). The heritability of ASD is estimated to be 50%. Whereas most of the inherited part of ASD is captured by common variants, our knowledge about the genetics of ASD comes almost exclusively from identification of highly penetrant de novo mutations through candidate gene or whole exome/genome sequencing studies. Approximately 10% of patients with ASD, especially those with intellectual disability, are carriers of de novo copy number or single nucleotide variants affecting clinically relevant genes for ASD. Because of the function of these genes, it was hypothesized that abnormal synaptic plasticity and failure of neuronal/synaptic homeostasis could increase the risk of ASD. It is hoped that this knowledge will lead to better diagnosis, care, and integration of individuals with ASD.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00002-9

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Genetics of X-Linked Intellectual Disability

Type de document :

texte imprimé

Auteurs :

Charles E. SCHWARTZ, Auteur ; Luigi BOCCUTO, Auteur

Année de publication :

2016

Importance :

p.25-41

Langues :

Anglais (eng)

Mots-clés :

Disease mechanisms Nonsyndromal XLID Syndromal XLID X-linked intellectual disability

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Intellectual disability (ID) represents a heterogeneous disorder affecting the development, function, and/or structure of the central nervous system. ID affects about 2–3% of the general population, with a male excess estimated around 30%. Genetic defects on the X chromosome are supposed to have a major role in this gender bias. X-linked intellectual disability (XLID) can be grouped into two categories, syndromal and nonsyndromal, although some genes can be responsible for both forms. In the past 2 decades, important progress has been made in identifying new causative genes and understanding the disease mechanisms underlying over 100 XLID conditions. Most known genes involve one of the following functional groups: presynaptic vesicle cycling and transport, cytoskeletal dynamics, cell adhesion and transsynaptic signaling, and translational regulation. Expanding knowledge of XLID also allows researchers to design new therapeutic approaches.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00003-0

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Genetic Causes of Intellectual Disability: The Genes Controlling Cortical Development

Type de document :

texte imprimé

Auteurs :

Yoann SAILLOUR, Auteur ; Jamel CHELLY, Auteur

Année de publication :

2016

Importance :

p.43-64

Langues :

Anglais (eng)

Mots-clés :

Brain cortex Cortical development Epilepsy Intellectual disability Malformations of cortical development (MCD) Neuronal migration disorders Tubulinopathies

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

The cerebral cortex has a key role in cognitive and intellectual processes. Its development results from careful orchestrated developmental interactions, most of which are unknown. In recent years, substantial insights have been gained through the rapid evolution of imaging techniques, large-scale genomic sequencing approaches, and the delineation of genes and mutations underlying neurodevelopmental disorders, including malformations of cortical development (MCDs), which are increasingly recognized as causes of intellectual disability conditions and epilepsy. Combined with investigation into cellular and animal models, genetic studies have identified genes, complexes, and pathways that might disrupt each of the main stages of cell proliferation, neuronal migration, and late cortical organization and lead to MCDs. This review summarizes most of the major MCDs from genetic and neurodevelopmental perspectives and highlights how understanding key molecular pathways can also lead to development of strategies aimed at reversing disrupted cellular and biological processes.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00004-2

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Immune Dysfunction in Autism Spectrum Disorder

Type de document :

texte imprimé

Auteurs :

Natalia V. MALKOVA, Auteur ; Elaine Y. HSIAO, Auteur

Année de publication :

2016

Importance :

p.65-82

Langues :

Anglais (eng)

Mots-clés :

Autoimmunity Maternal immune activation Microglia Neuroimmunology Neuroinflammation

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorder (ASD) is diagnosed based on abnormalities in social, communicative, and stereotyped behaviors, but a preponderance of evidence indicates that immune dysfunction is a key feature of ASD. In this chapter, we review the several cellular and functional immune alterations observed in the brains, periphery, and gastrointestinal tracts of ASD individuals. In addition, we highlight pathways for neuroimmune interactions and novel roles for immune factors in neurodevelopment. We further discuss immune-related environmental and genetic risk factors for ASD, along with findings from animal models that support a role for early life immune dysregulation in the etiopathogenesis of ASD symptoms. Finally, we outline results from clinical trials of immune-based therapies for ASD and consider future directions for investigating potential immune contributions to ASD diagnosis and treatment.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00005-4

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Synapse Proteomes and Disease: The MASC Paradigm

Type de document :

texte imprimé

Auteurs :

Àlex BAYES, Auteur ; Seth G. N. GRANT, Auteur

Année de publication :

2016

Importance :

p.85-99

Langues :

Anglais (eng)

Mots-clés :

Autism Cognition Intellectual disability Learning MAGUK MASC Proteomics Schizophrenia Synapse Synaptopathy

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

The synapse is composed of ∼2000 proteins, and mutations and genetic variants in these proteins result in a large number of disorders, collectively known as synaptopathies. A major subset of synapse proteins assemble with membrane-associated guanylate kinase (MAGUK) proteins into multiprotein complexes known as MAGUK-associated signaling complexes (MASCs). In total, 145 MASC genes have been related to 197 nervous system conditions. Cognitive behavioral disorders are prominent among these disorders, especially intellectual disability, autism, and schizophrenia. An extensive body of literature in mice has also demonstrated that mutations in MAGUK proteins result in cognitive impairments. Here we provide a detailed analysis of the genetic basis of MASC diseases. These comprehensive studies of synapse complexes and their roles in disease are a general paradigm linking proteomics, genetics, and molecular machines to brain disease.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00006-6

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

FMRP and the Pathophysiology of Fragile X Syndrome

Type de document :

texte imprimé

Auteurs :

Stephanie A. BARNES, Auteur ; Sophie R. THOMSON, Auteur ; Peter C. KIND, Auteur ; Emily K. OSTERWEIL, Auteur

Année de publication :

2016

Importance :

p.113-128

Langues :

Anglais (eng)

Mots-clés :

ERK FMR1 FMRP Fragile X mGluR1/5 Protein synthesis

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Fragile X syndrome (FXS) is a single-gene disorder that is the most prevalent heritable cause of intellectual disability and one of the most common single-gene causes of autism spectrum disorder (ASD). Although there is a clear genetic origin of FXS, there is still much to learn about the cellular and physiological consequences of FMR1 mutation. This knowledge is critical to the development of treatments to target the core pathophysiology of FXS. In this chapter, we summarize what is known about the function of the FMR1 gene and the encoded Fragile X mental retardation protein and describe the major cellular and neurophysiological phenotypes observed in the FXS mouse model. We then discuss evidence supporting the metabotropic glutamate receptor (mGluR) theory of Fragile X, which states that dysregulated protein synthesis downstream of mGluR1/5 is a core contributor to the pathogenesis of FXS. The remainder of the chapter will be devoted to discussing the clinical implications of this research and its relevance to the wider ASD population.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00008-X

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

X-Linked ASDs and ID Gene Mutations

Type de document :

texte imprimé

Auteurs :

Edoardo MORETTO, Auteur ; Maria PASSAFARO, Auteur ; Silvia BASSANI, Auteur

Année de publication :

2016

Importance :

p.129-150

Langues :

Anglais (eng)

Mots-clés :

MAGUK Small GTPase pathway Synapse X-LID X-Linked ASD

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Intellectual disability (ID) defines a group of disorders that cause impairment in intellectual performance. Autism spectrum disorders (ASDs) cause deficits in communication and social skills in addition to repetitive and stereotyped behaviors. We focus our attention on IDs and ASDs caused by mutations within the X chromosome on genes that exert their roles at the synapse. Notably, a significant overlap exists between ID and ASD in patients, likely mirroring the convergence of molecular pathways by which X-linked gene products regulate brain function. The genes described within are implicated in neuronal morphology, via cytoskeleton remodeling (genes belonging to the Rho GTPase pathway: OPHN1, ARHGEF6, and PAK3), in function, encoding receptor subunits (GRIA3), or acting to localize receptors and secondary messengers (ARHGEF9, TM4SF2, and the MAGUKs CASK and DLG3), and in presynaptic vesicle release (SYP, CASK, and genes belonging to the Rab GTPase pathway: RAB39B and GDI1).

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00009-1

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

The Function of MeCP2 and Its Causality in Rett Syndrome

Type de document :

texte imprimé

Auteurs :

Janine M. LAMONICA, Auteur ; Zhaolan ZHOU, Auteur

Année de publication :

2016

Importance :

p.101-112

Langues :

Anglais (eng)

Mots-clés :

Autism MeCP2 Mouse models Rett syndrome Synapse

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Methyl-CpG binding protein 2 (MeCP2) is a member of the methyl-CpG binding domain family of nuclear proteins with binding affinity for methylated deoxyribonucleic acid. Mutations in the X-linked MECP2 gene are the monogenic origin of Rett syndrome (RTT), a neurological disorder that is the most common cause of intellectual disability in young girls. After a period of normal development, patients lose learned language and motor skills and develop numerous symptoms including seizures, repetitive hand movements, respiratory irregularities, and autistic-like features. The pathogenic mechanisms by which dysfunction of the ubiquitously expressed MeCP2 leads to the unique symptoms of RTT have been intensely studied for 15 years. This chapter highlights the still-evolving concept of MeCP2 as a multifunctional protein and our current understanding of the molecular mechanisms and synaptic dysfunction underlying RTT through the study of Mecp2 mouse models.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00007-8

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder

Type de document :

texte imprimé

Auteurs :

Michael J. SCHMEISSER, Auteur ; Chiara VERPELLI, Auteur

Année de publication :

2016

Importance :

p.151-160

Langues :

Anglais (eng)

Mots-clés :

Autism spectrum disorder Intellectual disability Shank1 Shank2 Shank3 Synapse

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Mutations in the three human SHANK genes, which encode the postsynaptic scaffold proteins SHANK1, SHANK2, and SHANK3, are directly responsible for certain types of intellectual disability (ID) and in general for autism spectrum disorder (ASD). These neuropsychiatric conditions are caused by a generalized dysfunction of the brain, most probably owing to altered formation and plasticity of synaptic connections, thus leading to dysfunctional neuronal communication. Most interestingly, SHANK mutations affect individuals with a different grade of severity: that is, patients with SHANK3 mutations exhibit a strong ID and ASD phenotype, whereas patients with SHANK2 or SHANK1 mutations characteristically exhibit milder phenotypes. To summarize current knowledge about the effects of SHANK mutations on the pathogenesis of ID and ASD, we will discuss the impact of SHANK on synaptic function and highlight genotypic and phenotypic variations among mutations. Whereas the foundation of our knowledge on SHANK function began with in vitro studies, in vivo investigation of Shank mutant mice has further advanced our studies. Functional analysis of rodent Shank family members allows us to understand the role of these proteins better in brain development and in the pathogenesis of ID and ASD with the ultimate aim of identifying novel targets to develop effective therapies. With the recent discovery of human induced pluripotent stem cells, the ability to work on human neurons has opened up, potentially allowing for precise genetic mapping and possibly even personalized therapies to be developed. In this chapter, we will present an overview of SHANK function and SHANK mutations from the perspective of both in vitro and in vivo studies pointing to future directions where research on SHANK will likely go.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00010-8

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Mutations in Synaptic Adhesion Molecules

Type de document :

texte imprimé

Auteurs :

Jaewon KO, Auteur ; Caterina MONTANI, Auteur ; Eunjoon KIM, Auteur ; Carlo SALA, Auteur

Année de publication :

2016

Importance :

p.161-175

Langues :

Anglais (eng)

Mots-clés :

Excitatory synapse Inhibitory synapse Neurodevelopmental diseases Postsynaptic density Presynapse Synapse formation

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Synaptic connections are established between neurons during development of the nervous system after axon path finding and dendrite development. Synapse development is mediated by specific synaptic cell adhesion molecules (SCAMs) that accumulate at pre- and postsynaptic sites and trigger synaptic differentiation through interactions with intra- and extracellular proteins. These interactions are essential to align pre- and postsynaptic specializations and to couple the sites of cell-to-cell adhesion to the cytoskeletal and signaling complexes required to recruit and recycle presynaptic vesicles, components of exo- and endocytic zones, and postsynaptic receptors. Not surprisingly, it has been demonstrated that in humans, deletions or mutations in some of the SCAM genes are associated with several neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, and schizophrenia, although the exact connection between genetic background and biochemical mechanisms by which these mutations contribute to the diseases has been only partially revealed. This chapter describes the multiple functions and associated synaptic alterations of the SCAM genes found mutated in neurodevelopmental diseases.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00011-X

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

CNTNAP2 Mutations in Autism

Type de document :

texte imprimé

Auteurs :

Olga PENAGARIKANO, Auteur

Année de publication :

2016

Importance :

p.177-188

Langues :

Anglais (eng)

Mots-clés :

ASD Autism CDFE CNTNAP2 Social behavior

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASDs) comprise a phenotypically and genetically heterogeneous condition characterized by deficits in social behavior and communication together with the presence of repetitive and restrictive behaviors. Autism spectrum disorder has a strong genetic component and mutations/variants in many genes have been identified as predisposing to ASD. The contactin-associated protein-like 2 (CNTNAP2) gene is one of the most replicated through interdisciplinary studies, supported by neurobiological, genetic, and imaging data. An understanding of the mechanistic link between genes and behavior is critical to developing targeted treatments. This chapter discusses the clinical genetics and current understanding of the biology of CNTNAP2 as related to ASD. Current multidisciplinary research approaches in both human subjects and animal models help us understand the pathophysiology associated with the goal of developing new treatments.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00012-1

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Planar Cell Polarity Gene Mutations in Autism Spectrum Disorder, Intellectual Disabilities, and Related Deletion/Duplication Syndromes

Type de document :

texte imprimé

Auteurs :

Nathalie SANS, Auteur ; Jérôme EZAN, Auteur ; Maïté M. MOREAU, Auteur ; Mireille MONTCOUQUIOL, Auteur

Année de publication :

2016

Importance :

p.189-219

Langues :

Anglais (eng)

Mots-clés :

Autism Developmental delay Gene network Intellectual disabilities NTD PCP Scribble

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

In this chapter, we focus on inherited or de novo human mutations associated with autism spectrum disorder (ASD) or intellectual disability (ID) disorder, which involve members of the noncanonical planar cell polarity (PCP) pathway(s). Although most of these gene mutations give rise to multisystemic phenotypes, some mutations are involved in monogenic disorders. In the past 15 years, whereas they have been studied mostly in invertebrates, the involvement of PCP genes in numerous functions in mammals has been identified. Planar cell polarity genes have been implicated in brain development, sensory functions, synaptic plasticity, learning and memory, and social behavior, to cite a few. Thus, it is not surprising, given their impact on many crucial cellular functions, that by sequencing the exomes of ASD patients and their parents for studies of single nucleotide polymorphism association, global rare copy number variation, rare de novo variants, or de novo mutations, some PCP genes have emerged as susceptibility genes in ASD or ID syndromes and related pathologies.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00013-3

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Protocadherin Mutations in Neurodevelopmental Disorders

Type de document :

texte imprimé

Auteurs :

Duyen PHAM, Auteur ; Chuan TAN, Auteur ; Claire HOMAN, Auteur ; Lachlan JOLLY, Auteur ; Jozef GECZ, Auteur

Année de publication :

2016

Importance :

p.221-231

Langues :

Anglais (eng)

Mots-clés :

Adhesion molecule Mutation Neurodevelopmental disorder PCDH19 Protocadherin

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Neurodevelopmental disorders such as intellectual disability (ID), epilepsy, autism spectrum disorders (ASDs), schizophrenia (SZ), and bipolar disorder (BD) include cognitive, neurological, and/or psychiatric dysfunction and can be caused by impairment of the brain during development. These disorders are complex and highly heterogeneous and often coexist with other types of co-comorbidities. Mutations in genes encoding for cell adhesion molecules, specifically the delta-2-protocadherin (δ2-PCDH) family have been shown to be associated with a number of these disorders. These genes have crucial roles in early brain development, including neuronal migration, synaptogenesis, and axonal growth. Currently, little is known about how mutations in the protocadherin gene family contribute to the underlying pathogenesis of neurodevelopmental disorders. This review will discusses different neurodevelopmental disorders and the role of their respective associated published δ2-PCDHs mutations, in particular PCDH19, including new insights into novel mutations potentially contributing to these diseases.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00014-5

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Mutations of Voltage-Gated Sodium Channel Genes SCN1A and SCN2A in Epilepsy, Intellectual Disability, and Autism

Type de document :

texte imprimé

Auteurs :

Kazuhiro YAMAKAWA, Auteur

Année de publication :

2016

Importance :

p.233-251

Langues :

Anglais (eng)

Mots-clés :

Autism Dravet syndrome Epilepsy Intellectual disability Nav1.1 Nav1.2 Parvalbumin inhibitory neuron SCN1A SCN2A Sodium channel

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Mutations of SCN1A and SCN2A were found in a wide spectrum of epilepsies, intellectual disability, and autism. Nav1.1 protein encoded by SCN1A is densely expressed in parvalbumin-positive inhibitory interneurons and moderately in a subpopulation of excitatory neurons. Dravet syndrome model mice (SCN1A+/−) showed epileptic seizure, sudden death, and autistic behavior similar to patients, and conditional knockout mice studies revealed that Nav1.1 haploinsufficiency in inhibitory neurons is the primary cause for those features and that in excitatory neurons it is contrarily ameliorating for seizures and sudden death. Whole-exome sequencing studies on hundreds of autistic patients also showed SCN1A de novo loss of function mutations, but those of SCN2A were far more dominated. SCN2A mutations also appear in patients with epileptic encephalopathies, but those are mostly missense suggesting gain-of-function. Dominant expression of Nav1.2 encoded by SCN2A in excitatory neurons may explain the afebrile nature of the disease and suggest distinct pathological cascades for those with SCN1A mutations.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00015-7

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Oxytocin in the Developing Brain: Relevance as Disease-Modifying Treatment in Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Bice CHINI, Auteur ; Marianna LEONZINO, Auteur ; Valentina GIGLIUCCI, Auteur

Année de publication :

2016

Importance :

p.253-266

Langues :

Anglais (eng)

Mots-clés :

Autism Monoamines Neurodevelopment Opioid Oxytocin Oxytocin receptor Perinatal treatment Social behavior

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Among the several neurobiological systems implicated in shaping social behavior, oxytocin (OXT) has been firmly established as a master regulator of the social brain. This has led OXT to be proposed as a drug to ameliorate social deficits in a number of neurodevelopmental and neuropsychiatric conditions including autism spectrum disorders (ASDs). OXT administration has indeed been shown to improve social symptoms in adult ASD patients; even more interestingly, OXT has been shown to regulate key neurodevelopmental events, which suggests that the peptide can modify the onset and progression of ASD symptoms in childhood. We will review here the anatomical and neurochemical basis of these actions, with a special emphasis on the interactions of OXT with other key neurotransmitter systems involved in the regulation of social behavior at the early postnatal developmental stages.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00016-9

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Mouse Behavior and Models for Autism Spectrum Disorders

Type de document :

texte imprimé

Auteurs :

Laura RICCERI, Auteur ; Caterina MICHETTI, Auteur ; Maria Luisa SCATTONI, Auteur

Année de publication :

2016

Importance :

p.269-293

Langues :

Anglais (eng)

Mots-clés :

Mouse behavior Mouse models Mutants Olfactory tests Repetitive behaviors Social approach Social communication Social interaction

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Autism spectrum disorders (ASDs) are behaviorally defined disorders including attenuated or abnormal social interaction and communication, as well as aberrant repetitive behavior, with symptoms emerging early in childhood. Although the cause of autism has not been discovered, several data strongly support the role of genetic factors in its etiology. For this reason, preclinical research has focused on transgenic and knockout mice bearing mutations in genes identified in autistic children, with the aim of understanding the role of those genes in autism etiology, discovering the biological mechanisms underlying behavioral alterations observed and evaluating potential treatments. In past years, a number of behavioral phenotyping assays for rodent models of autism and related disorders have been developed. In the first part of our review, we describe these behavioral paradigms currently used in ASD rodent models; the second part is an overview of valid and robust animal models of ASD.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00017-0

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

The iPSC Technology to Study Neurodevelopmental Disorders

Type de document :

texte imprimé

Auteurs :

Alysson Renato MUOTRI, Auteur

Année de publication :

2016

Importance :

p.295-300

Langues :

Anglais (eng)

Mots-clés :

Autism spectrum disorders Brain Disease modeling Drug screening Human induced pluripotent stem cells Human neurons

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

The inaccessibility of live human brain cells for research has blocked progress toward understanding mechanisms underlying neurodevelopmental disorders. A human model, using reprogrammed patient somatic cells offers an attractive alternative because it captures a patient's genome in a pluripotent stage. Despite current pitfalls, the disease-in-a-dish approach allows dynamic analyses of target cells, offering a unique opportunity to dissect cellular and molecular alterations in a controlled environment. Recent publications have highlighted the use of induced pluripotent stem cells (iPSCs) to model autism spectrum disorders (ASDs). Here, I will discuss the advantages of the iPSC technology to complement and advance the research in ASD. Furthermore, I will review the literature on upcoming innovative technology in tissue engineering and examine how that could be combined with current stem cell practices for a better disease modeling tool and future drug screening.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00018-2

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Rett Syndrome: Clinical Aspects

Type de document :

texte imprimé

Auteurs :

Daniel C. TARQUINIO, Auteur ; Alan K. PERCY, Auteur

Année de publication :

2016

Importance :

p.301-323

Langues :

Anglais (eng)

Mots-clés :

Communication disorders Disease management Epidemiology Growth failure MECP2 Molecular targeted therapy Neurobiology Rett syndrome

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Rett syndrome (RTT) affects 1:10,000 females, causing psychomotor regression and stereotypical hand movements. In the past half century, many clinical, neurobiological, and genetic aspects of RTT have been clarified, including identification of methyl CpG binding protein 2 gene mutations in most. Although loss of language and hand function and problems with ambulation are core disabilities in the disorder, a host of comorbidities affect girls and women with RTT. A Rett specialist typically works closely with other medical professionals, including therapists, nutritionists, social workers, and medical consultants related to the various systems affected. Most girls have problems that require the help of a neurologist or epileptologist, a gastroenterologist, and an orthopedic surgeon, and many require endocrinology and cardiology consultation. Within the past few years, an explosion in the investigation of disease-specific treatments has occurred, and targeted drugs will soon be available to help girls and women with RTT.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00019-4

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Fragile X Syndrome

Type de document :

texte imprimé

Auteurs :

Anne HOFFMANN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur

Année de publication :

2016

Importance :

p.325-346

Langues :

Anglais (eng)

Mots-clés :

Autism spectrum disorder FMR1 FMRP Fragile X syndrome Intellectual disability

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Fragile X syndrome (FXS) is recognized as the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASDs), with many overlapping phenotypic features. Fragile X syndrome is caused by absence or reduction of expression of the fragile X mental retardation protein and is associated with a variety of behavioral, physical, and medical problems, which are managed through supportive treatment, often incorporating psychopharmacology to ameliorate limiting behaviors. Specific patterns of cognitive, language, and adaptive strengths and weaknesses are typically present and can be used to tailor educational and therapeutic programming to the needs of the individual with FXS. Recent major advances in the understanding of the underlying neurobiology in FXS have led to the discovery of agents that rescue phenotypes in the FXS mouse model and to early clinical trials of targeted treatments in humans with FXS. Thus, translational strategies in FXS may serve as models for ASD and other cognitive disorders.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00020-0

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Phelan-McDermid Syndrome: Clinical Aspects

Type de document :

texte imprimé

Auteurs :

Katy PHELAN, Auteur ; Luigi BOCCUTO, Auteur ; Sara SARASUA, Auteur

Année de publication :

2016

Importance :

p.347-364

Langues :

Anglais (eng)

Mots-clés :

22q13 deletion Absent speech Autism Dysplastic toenails Hypotonia Intellectual impairment Phelan–McDermid SHANK3 Speech delay

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

Phelan–McDermid syndrome (PMS), also known as the 22q13 deletion syndrome, is a genetic condition characterized by neonatal hypotonia, developmental delay, absent or impaired speech, and minor dysmorphic features. PMS typically results from a deletion of the distal long arm of chromosome 22, with the size of the deleted segment ranging from less than 100 kb to greater than 9 MB. The loss of 22q13 may result from a terminal deletion, an interstitial deletion, an unbalanced translocation, formation of a ring chromosome, or other types of structural chromosome aberrations. In most cases, the deletion results in haploinsufficiency for the SHANK3 gene which codes for a scaffolding protein in the postsynaptic density of excitatory neurons. Mutation or disruption of the SHANK3 gene may also result in PMS. The diagnosis of PMS relies on laboratory confirmation by molecular cytogenetic or molecular genetic methods.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00021-2

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Titre :

Epilepsy Associated with ASD and Intellectual Disability

Type de document :

texte imprimé

Auteurs :

Carla MARINI, Auteur

Année de publication :

2016

Importance :

p.365-373

Langues :

Anglais (eng)

Mots-clés :

Autism spectrum disorder Chromosomal rearrangements Epilepsy Genetic Seizures

Index. décimale :

SCI-D SCI-D - Neurosciences

Résumé :

The co-occurrence of autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy is well established among clinicians and researchers. Epilepsy is reported to occur in ASD, with a prevalence ranging from 5% to 46%. Among patients with epilepsy, ASD symptoms may occur in 15–35% of children and about a quarter will also have ID. Epilepsy onset shows a bimodal curve with a first peak before 5 years of age and a second during adolescence. Seizures may be either focal or generalized including infantile spasms. Epileptic encephalopathies in addition to intractable seizures often manifest ID and ASD. The frequent association among epileptic, ID, and autistic phenotypes suggests that these disorders may share common predisposing genes. Molecular genetic studies and, more recently, whole-exome sequencing have indeed shown that mutations of specific genes may cause ASD, seizures, and ID, which confirms the common underlying pathophysiological mechanism at least in some patients.

En ligne :

http://dx.doi.org/10.1016/B978-0-12-800109-7.00022-4

Permalink :

https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Exemplaires(0)

Disponibilité
aucun exemplaire

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(1)

Centre d'Information et de Documentation
du CRA Rhône-Alpes

Accueil

Se connecter

Adresse

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(0)

Exemplaires(1)

Centre d'Information et de Documentation du CRA Rhône-Alpes

Accueil

Se connecter

Adresse

Centre d'Information et de Documentation
du CRA Rhône-Alpes