3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Iourov, Ivan; Vorsanova, Svetlana; Voinova, Victoria; Yurov, Yuri
• Is Part Of: Molecular cytogenetics. Volume 8:Issue 1(2015)
• Page Start: 1
• Page End: 6
• Publication Date: 2015-12
• Subjects: Asperger syndrome -- Autism -- Bioinformatics -- Chromosome abnormality -- Therapeutic strategy -- Candidate gene -- Zinc; Cytogenetics -- Periodicals; Chromosomes -- Periodicals; Molecular genetics -- Periodicals; 572.805
• DOI: 10.1186/s13039-015-0185-9
• Languages: English
• ISSNs: 1755-8166

Abstract

Abstract 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. Furtherin 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 identifiedCCK (cholecystokinin) as a candidate gene for AS. In addition to processes associated with deleted genes, bioinformatic analysis ofCCK 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.