The interrelationship between the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule-Generic (ADOS-G) and clinical classification was studied in 184 children and adolescents with Mental Retardation (MR). The agreement between the ADI-R and ADOS-G was fair, with a substantial difference between younger and older children (5-8 vs. 8+ years). Compared with the Diagnostic and Statistical Manual of Mental Disorders-IV-TR (DSM-IV-TR) classification of Autistic Disorder (AD) and Pervasive Developmental Disorder (PDD), both instruments measure AD or PDD validly and reliably. Even in low-functioning children the interrelationship between the instruments and the clinical classification was satisfactory. The combination of ADI-R and ADOS-G identifies AD or PDD, as described in the DSM-IV-TR, most appropriately. Both instruments seem to be of great value in the diagnostic process of PDD in children and adolescents with MR.

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Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family.

Pragmatic difficulties do occur in both HFA and ADHD. The present studies indicate that the CCC is a useful instrument to obtain information concerning pragmatic language use in both a clinical and a research setting. Although the information of parents is more tightly linked to the diagnosis, combining the information of both parent and teacher slightly improves case identification.

Background Autism-spectrum disorders (ASD) are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. Based on results of prior genetic linkage studies and reported altered innate immune response in ASD, we hypothesized that MIF could represent a candidate gene for ASD or its diagnostic components. Methods Genetic association between ASD and MIF was investigated in two independent sets of families of probands with ASD, from USA (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for ASD diagnoses. Genotyping was performed for two polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were carried out in a subset of Dutch patients from whom plasma was available. Results There were genetic associations between known functional polymorphisms in the promoter for MIF and ASD-related behaviors. Also, probands with ASD exhibited higher circulating MIF levels than did their unaffected siblings; the amount of MIF in the plasma correlated with the severity of multiple ASD symptoms. Conclusions These results identify MIF as a susceptibility gene for ASD. Further research is warranted on the precise relationship between MIF and the behavioral components of ASD, the mechanism by which MIF contributes to ASD pathogenesis, and the clinical utility of MIF genotyping.