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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. © 2005 Wiley-Liss, Inc.

PURPOSE: To compare the ability of qualitative fludeoxyglucose F 18 positron emission tomography (QPET), qualitative MR imaging (QMR), and quantitative MR imaging with hippocampal formation volumetric assessment (HV MR) to lateralize the seizure focus in patients with temporal lobe epilepsy. METHODS: Sixteen consecutive patients undergoing presurgical examination for temporal lobe seizures had QPET, QMR, and HV MR. The presence of temporal lobe epilepsy was confirmed by Engel class I or II outcomes at 1-year postoperative follow-up examinations. A QPET, QMR, or HV MR study was considered to be lateralizing if it matched the side of the seizure focus, nonlateralizing if it did not lateralize the seizure focus to either temporal lobe, or incorrectly lateralizing if it lateralized the seizure focus to the incorrect side. RESULTS: Of 16 patients with proved temporal lobe seizures, QPET was correctly lateralizing in nine (56%), nonlateralizing in six (37.5%), and incorrectly lateralizing in one (6%). QMR was correctly lateralizing in six (37.5%), nonlateralizing in six (37.5%), and incorrectly lateralizing in four (25%). HV MR was correctly lateralizing in all 16 patients (100%). Age at onset, seizure duration, and total number of seizures did not correlate with QPET, QMR, and HV MR lateralization. CONCLUSIONS: Our results show that each imaging technique yields useful information for seizure lateralization in temporal lobe epilepsy and that HV MR yields considerably more information that QPET or QMR.