CES effectively identified disease-causing alleles at the mild end of the cohensinopathy spectrum and enabled characterization of candidate disease genes.

Autism is a highly heritable neurodevelopmental syndrome with a complex genetic etiology for which no disease genes have yet been definitively identified. We ascertained three subjects with autism spectrum disorders and chromosome 2q37.3 terminal deletions, and refined the deletion breakpoint regions using polymorphism mapping and fluorescence in situ hybridization (FISH) probes. We then genotyped polymorphic markers downstream from the breakpoint region in a sample of autism affected sibling pair families. Both the chromosomal breakpoints and linkage analyses focused our attention on the gene centaurin gamma-2 (CENTG2), an attractive candidate gene based also on its function and pattern of expression. We therefore assessed CENTG2 for its involvement in autism by (1) screening its exons for variants in 199 autistic and 160 non-autistic individuals, and (2) genotyping and assessing intra-genic polymorphisms for linkage and linkage disequilibrium (LD). The exon screen revealed a Ser ! Gly substitution in one proband, an Arg ! Gly substitution in another, and a number of additional variants unique to the autism families. No unique variants were found in the control subjects. The genotyping produced strong evidence for linkage from two intronic polymorphisms, with a maximum two-point HLOD value of 3.96 and a posterior probability of linkage (PPL) of 51%. These results were contradicted, however, by substantially weaker evidence for linkage from multi-point analyses and by no evidence of LD. We conclude, therefore, that 2q37.3 continues to be a region of interest for autism susceptibility, and that CENTG2 is an intriguing candidate gene that merits further scrutiny for its role in autism.

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Recent Conversation Analytic work has revealed that there are systematic differences between the ways in which patients with epilepsy and patients with "psychogenic" non-epileptic seizures (NES) describe their seizure experiences. But these differences may not become apparent if patients are exposed to traditional fact-oriented questioning. This article describes a oneday intervention workshop, informed by Conversation Analysis, which was designed to help doctors change their history-taking style and solicit diagnostically useful narrative features. A comparison of video-recordings of 38 routine consultations before the intervention, and 20 consultations after it, showed that the intervention had the desired effect. Doctors' problem presentation solicitation changed, and the patient responses were better suited to revealing diagnostically-relevant features of their talk. Data in British English.