Williams-Beuren syndrome is a neurodevelopmental disorder mainly characterized by dysmorphic features, vascular stenoses, abnormalities of calcium and glucose metabolism, and mental retardation with visuospatial deficits, caused by de novo deletion of 26-28 genes at 7q11.23. Clinical-molecular correlations have defined critically deleted genes as likely responsible for several aspects of the phenotype, but the precise biological pathways affected are mostly unknown. We performed comparative transcriptome profiling of lymphoblastoid cell lines from four Williams-Beuren syndrome patients and two patients with smaller deletions and partial phenotypes. We detected 92 genes deregulated in all patients and 47 genes deregulated only in Williams-Beuren syndrome, with two additional clusters differentially expressed between both groups. Glycolysis and neuronal migration were the most significantly affected pathways by over-representation analyses. In addition, several genes involved in microtubule formation were specifically deregulated in patients with the common deletion. In summary, comparative expression profiling in lymphoblasts has revealed abnormal regulation of gene pathways potentially related to relevant aspects of the Williams-Beuren syndrome phenotype, including the cognitive, visuospatial and metabolic disturbances.
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