The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders

Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relat...

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Published inTrends in neurosciences (Regular ed.) Vol. 32; no. 7; pp. 402 - 412
Main Authors Betancur, Catalina, Sakurai, Takeshi, Buxbaum, Joseph D.
Format Journal Article
LanguageEnglish
Published Amsterdam Elsevier Ltd 01.07.2009
Elsevier
Elsevier Sequoia S.A
Subjects
Animals
Autism
Autistic Disorder - genetics
Autistic Disorder - metabolism
Autistic Disorder - pathology
Biological and medical sciences
Cell adhesion & migration
Cell Adhesion - genetics
Cell Adhesion - physiology
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - physiology
Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...)
Fundamental and applied biological sciences. Psychology
General aspects. Models. Methods
Genetic Predisposition to Disease - genetics
Genetics
Genomics
Humans
Life Sciences
Medical genetics
Medical sciences
Neurology
Neurons
Neurosciences
Signal Transduction - genetics
Signal Transduction - physiology
Synapses - genetics
Synapses - physiology
Vertebrates: nervous system and sense organs
Human
Chromosome fragility
Animal model
High risk
Nervous system diseases
Pathogenesis
Genetic variant
Developmental disorder
Review
Genetic disease
Cerebral disorder
Autism
Validity
Pervasive developmental disorder
Central nervous system disease
Rett syndrome
Tumor
Degenerative disease
Bourneville syndrome
Fragile X syndrome
mutation
copy number variation
gene
deletion
cell adhesion molecule
synapse
autism spectrum disorder
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Abstract Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, including those involving synaptic cell adhesion, are disrupted in some subjects with ASD. These findings provide insights into the pathogenesis of ASDs and enable the development of model systems with construct validity for specific causes of ASDs. In several neurodevelopmental disorders frequently associated with ASD, including fragile X syndrome, Rett syndrome and tuberous sclerosis, animal models have led to the development of new therapeutic approaches, giving rise to optimism with other causes of ASDs.
AbstractList Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, including those involving synaptic cell adhesion, are disrupted in some subjects with ASD. These findings provide insights into the pathogenesis of ASDs and enable the development of model systems with construct validity for specific causes of ASDs. In several neurodevelopmental disorders frequently associated with ASD, including fragile X syndrome, Rett syndrome and tuberous sclerosis, animal models have led to the development of new therapeutic approaches, giving rise to optimism with other causes of ASDs.
Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, including those involving synaptic cell adhesion, are disrupted in some subjects with ASD. These findings provide insights into the pathogenesis of ASDs and allow for the development of model systems with construct validity for specific causes of ASDs. In several neurodevelopmental disorders frequently associated with ASD, including fragile X syndrome, Rett syndrome, and tuberous sclerosis, animal models have led to the development of new therapeutic approaches, giving rise to optimism with other causes of ASDs.
Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, including those involving synaptic cell adhesion, are disrupted in some subjects with ASD. These findings provide insights into the pathogenesis of ASDs and enable the development of model systems with construct validity for specific causes of ASDs. In several neurodevelopmental disorders frequently associated with ASD, including fragile X syndrome, Rett syndrome and tuberous sclerosis, animal models have led to the development of new therapeutic approaches, giving rise to optimism with other causes of ASDs.Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, including those involving synaptic cell adhesion, are disrupted in some subjects with ASD. These findings provide insights into the pathogenesis of ASDs and enable the development of model systems with construct validity for specific causes of ASDs. In several neurodevelopmental disorders frequently associated with ASD, including fragile X syndrome, Rett syndrome and tuberous sclerosis, animal models have led to the development of new therapeutic approaches, giving rise to optimism with other causes of ASDs.
Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations. These findings support a novel view of ASDs in which many independent, individually rare genetic variants, each associated with a very high relative risk, together explain a large proportion of ASDs. Although these rare variants impact diverse pathways, there is accumulating evidence that synaptic pathways, including those involving synaptic cell adhesion, are disrupted in some subjects with ASD. These findings provide insights into the pathogenesis of ASDs and enable the development of model systems with construct validity for specific causes of ASDs. In several neurodevelopmental disorders frequently associated with ASD, including fragile X syndrome, Rett syndrome and tuberous sclerosis, animal models have led to the development of new therapeutic approaches, giving rise to optimism with other causes of ASDs. [PUBLICATION ABSTRACT]
Author Betancur, Catalina
Sakurai, Takeshi
Buxbaum, Joseph D.
AuthorAffiliation 2 Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
1 INSERM U952, Université Pierre et Marie Curie, Paris 75005, France
4 Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
8 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
6 Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
3 the Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, New York 10029, USA
5 Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029, USA
7 Department of Neuroscience, and Mount Sinai School of Medicine, New York, New York 10029, USA
AuthorAffiliation_xml – name: 7 Department of Neuroscience, and Mount Sinai School of Medicine, New York, New York 10029, USA
– name: 5 Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029, USA
– name: 2 Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
– name: 3 the Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, New York 10029, USA
– name: 4 Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA
– name: 8 Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
– name: 1 INSERM U952, Université Pierre et Marie Curie, Paris 75005, France
– name: 6 Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
Author_xml – sequence: 1
  givenname: Catalina
  surname: Betancur
  fullname: Betancur, Catalina
  organization: INSERM U952, Université Pierre et Marie Curie, Paris 75005, France
– sequence: 2
  givenname: Takeshi
  surname: Sakurai
  fullname: Sakurai, Takeshi
  organization: Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA
– sequence: 3
  givenname: Joseph D.
  surname: Buxbaum
  fullname: Buxbaum, Joseph D.
  email: joseph.buxbaum@mssm.edu
  organization: Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA
BackLink http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21858714$$DView record in Pascal Francis
https://www.ncbi.nlm.nih.gov/pubmed/19541375$$D View this record in MEDLINE/PubMed
https://inserm.hal.science/inserm-00401195$$DView record in HAL
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Issue 7
Keywords Human
Chromosome fragility
Animal model
High risk
Nervous system diseases
Pathogenesis
Genetic variant
Developmental disorder
Review
Genetic disease
Cerebral disorder
Autism
Validity
Pervasive developmental disorder
Central nervous system disease
Rett syndrome
Tumor
Degenerative disease
Bourneville syndrome
Fragile X syndrome
mutation
copy number variation
gene
deletion
cell adhesion molecule
synapse
autism spectrum disorder
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Snippet Recent advances in genetics and genomics have unveiled numerous cases of autism spectrum disorders (ASDs) associated with rare, causal genetic variations....
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SubjectTerms Animals
Autism
Autistic Disorder - genetics
Autistic Disorder - metabolism
Autistic Disorder - pathology
Biological and medical sciences
Cell adhesion & migration
Cell Adhesion - genetics
Cell Adhesion - physiology
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - physiology
Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...)
Fundamental and applied biological sciences. Psychology
General aspects. Models. Methods
Genetic Predisposition to Disease - genetics
Genetics
Genomics
Humans
Life Sciences
Medical genetics
Medical sciences
Neurology
Neurons
Neurosciences
Signal Transduction - genetics
Signal Transduction - physiology
Synapses - genetics
Synapses - physiology
Vertebrates: nervous system and sense organs
Title The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders
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Volume 32
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