title: [Genotype/phenotype correlation in autism: genetic models and phenotypic characterization].
abstract: BACKGROUND
  Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established.
  
  
  RESULTS
  To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of "Broad Autism Phenotype" related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However, strategies useful to characterize such phenotypic markers (for example, electrophysiological markers) have to take into account that autism is an early neurodevelopmental disorder occurring during childhood when brain development and maturation are in process.
  
  
  CONCLUSIONS
  Recent genetic results have improved our knowledge in genetic basis in autism. Nevertheless, correspondences with phenotypic markers remain challenging according to phenotypic and genotypic heterogeneity.
authors.affiliation: Unité Inserm 930, imagerie et cerveau, Équipe 1 autisme et troubles du développement: psychopathologie, physiopathologie et thérapeutique, centre universitaire de pédopsychiatrie, CHRU de Tours, 2, boulevard Tonnellé, 37000 Tours, France. f.bonnet-brilhault@chu-tours.fr
authors.forename: F
authors.initials: F
authors.lastname: Bonnet-Brilhault
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002648:Child; D015897:Comorbidity; D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000235:genetics / Q000523:psychology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D020412:Multifactorial Inheritance; D010641:Phenotype; D012307:Risk Factors; D012931:Social Environment; D013223:Statistics as Topic