3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances.

Background: In contrast to other autism spectrum disorders, chromosome abnormalities are rare in Asperger syndrome (AS) or high-functioning autism. Consequently, AS was occasionally subjected to classical positional cloning. Here, we report on a case of AS associated with a deletion of the short arm of chromosome 3. Further in silico analysis has identified a candidate gene for AS and has suggested a therapeutic strategy for manifestations of the chromosome rearrangement.

Results: Using array comparative genomic hybridization, an interstitial deletion of 3p22.1p21.31 (~2.5 Mb in size) in a child with Asperger's syndrome, seborrheic dermatitis and chronic pancreatitis was detected. Original bioinformatic approach to the prioritization of candidate genes/processes identified CCK (cholecystokinin) as a candidate gene for AS. In addition to processes associated with deleted genes, bioinformatic analysis of CCK gene interactome indicated that zinc deficiency might be a pathogenic mechanism in this case. This suggestion was supported by plasma zinc concentration measurements. The increase of zinc intake produced a rise in zinc plasma concentration and the improvement in the patient's condition.

Conclusions: Our study supported previous linkage findings and had suggested a new candidate gene in AS. Moreover, bioinformatic analysis identified the pathogenic mechanism, which was used to propose a therapeutic strategy for manifestations of the deletion. The relative success of this strategy allows speculating that therapeutic or dietary normalization of metabolic processes altered by a chromosome imbalance or genomic copy number variations may be a way for treating at least a small proportion of cases of these presumably incurable genetic conditions.