Expanding the clinical phenotype at the 3q13.31 locus with a new case of microdeletion and first characterization of the reciprocal duplication

More interestingly, we report for the first time the existence of a microduplication reciprocal to the microdeletion syndrome. This familial 2.76 Mb microduplication identified by array-CGH was carried by two brothers and their father. The phenotype shared by the brothers resembled the phenotype related to the 3q13.31 microdeletion syndrome including especially severe intellectual disability, developmental delay, behavioral abnormalities and obesity. This microduplication involves three strong candidate genes for the developmental delay ZBTB20, LSAMP and GAP43. Further molecular characterization showed that DRD3, another strong candidate gene for developmental delay, was not included in the duplicated region. However, a dosage alteration of this gene cannot be completely excluded as the duplication was inverted at proximity of this gene, as revealed by FISH analysis. Finally, we hypothesized that the phenotype shared by the two brothers could be related to a gene dosage imbalance even if gene expression could not be measured in relevant tissues such as brain or adipocytes.