[Autism, genetics and synaptic function alterations].
Autism is a neurodevelopmental disorder characterized by a deficit of language and communication both associated with a restricted repertoire of activities and interests. The current prevalence of autistic disorder stricto sensu is estimated at 1/500 whereas autism spectrum disorders (ASD) increases up to 1/150 to 1/200. Mental deficiency (MD) and epilepsy are present in numerous autistic individuals. Consequently, autism is as a major public health issue. Autism was first considered as a non biological disease; however various rational approaches for analysing epidemiological data suggested the possibility of the influence of genetic factors. In 2003, this hypothesis was clearly illustrated by the characterization of genetic mutations transmitted through a mendelian manner. Subsequently, the glutamate synapse appeared as a preferential causal target in autism because the identified genes encoded proteins present in this structure. Strikingly, the findings that an identical genetic dysfunction of the synapse might also explain some MD suggested the possibility of a genetic comorbidity between these neurodevelopmental conditions. To date, various identified genes are considered indifferently as "autism" or "MD" genes. The characterization of mutations in the NLGN4X gene in patients with Asperger syndrome, autism without MD, or MD without autism, was the first example. It appears that a genetic continuum between ASD on one hand, and between autism and MD on the other hand, is present. Consequently, it is likely that genes already involved in MD will be found mutated in autistic patients and will represent future target for finding new factors in autism.
Perche
O
O
UMR 6218, CNRS, IEM, Équipe Génétique Expérimentale et Moléculaire, Université d'Orléans, 3B, rue de la Férollerie, 45071 Orléans-La-Source cedex 2, France.
Laumonnier
F
F
Baala
L
L
Ardourel
M-Y
MY
Menuet
A
A
Robin
V
V
Mortaud
S
S
Montécot-Dubourg
C
C
Richard
O
O
Pichon
J
J
Briault
S
S
D020817:Asperger Syndrome / Q000235:genetics / Q000503:physiopathology; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001321:Autistic Disorder / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics; D015897:Comorbidity; D004827:Epilepsy / Q000453:epidemiology / Q000235:genetics; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D015994:Incidence; D008607:Intellectual Disability / Q000453:epidemiology / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; C430845:NLGN4X protein, human; D017470:Receptors, Glutamate; D018698:Glutamic Acid