RESUMO
OBJECTIVE: Autism displays a remarkably high heritability but a complex genetic etiology. One approach to identifying susceptibility loci under these conditions is to define more homogeneous subsets of families on the basis of genetically relevant phenotypic or biological characteristics that vary from case to case. METHOD: The authors performed a principal components analysis, using items from the Autism Diagnostic Interview, which resulted in six clusters of variables, five of which showed significant sib-sib correlation. The utility of these phenotypic subsets was tested in an exploratory genetic analysis of the autism candidate region on chromosome 15q11-q13. RESULTS: When the Collaborative Linkage Study of Autism sample was divided, on the basis of mean proband score for the "savant skills" cluster, the heterogeneity logarithm of the odds under a recessive model at D15S511, within the GABRB3 gene, increased from 0.6 to 2.6 in the subset of families in which probands had greater savant skills. CONCLUSIONS: These data are consistent with the genetic contribution of a 15q locus to autism susceptibility in a subset of affected individuals exhibiting savant skills. Similar types of skills have been noted in individuals with Prader-Willi syndrome, which results from deletions of this chromosomal region.
Assuntos
Transtorno Autístico/genética , Cromossomos Humanos Par 15/genética , Cognição/fisiologia , Ligação Genética , Transtorno Autístico/diagnóstico , Transtorno Autístico/metabolismo , Criança , Análise Fatorial , Feminino , Expressão Gênica/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fenótipo , Receptores de GABA/genética , Receptores de GABA/metabolismoRESUMO
OBJECTIVE: To develop factors based on the Autism Diagnostic Interview-Revised (ADI-R) that index separate components of the autism phenotype that are genetically relevant and validated against standard measures of the constructs. METHOD: ADIs and ADI-Rs of 292 individuals with autism were subjected to a principal components analysis using VARCLUS. The resulting variable clusters were validated against standard measures. RESULTS: Six clusters of variables emerged: spoken language, social intent, compulsions, developmental milestones, savant skills and sensory aversions. Five of the factors were significantly correlated with the validating measures and had good internal consistency, face validity, and discriminant and construct validity. Most intraclass correlations between siblings were adequate for use in genetic studies. CONCLUSION: The ADI-R contains correlated clusters of variables that are valid, genetically relevant, and that can be used in a variety of studies.